Protein-tyrosine kinases participate in a variety of signal transduction pathways that modulate cell growth and differentiation (1, 2, 3) . Signal transduction is triggered by stimulation of a cell-surface receptor that either has kinase activity itself or is physically and/or functionally linked to an intracellular protein-tyrosine kinase(4, 5, 6) . The integrins are also capable of transducing cytoplasmic signals(7, 8, 9) , and activation of this pathway is linked to one or more protein-tyrosine kinases(10, 11) . A nonreceptor cytosolic tyrosine kinase, termed the focal adhesion kinase (pp125), has been identified as one of the cellular proteins that is phosphorylated in response to - and -integrin-mediated cell adhesion(8, 12, 13, 14, 15) . Induction of the kinase activity and tyrosine phosphorylation of pp125 were observed following the adherence of fibroblasts to fibronectin(10, 11, 12, 13, 14, 15, 16) ; the adherence of epidermal carcinoma cells to fibronectin, laminin, or collagen type IV(17) ; and the aggregation of platelets in the presence of fibrinogen, a ligand for -integrin (glycoprotein IIb/IIIa)(18) . Phosphorylated pp125 is localized in focal adhesion contacts.

pp125 has been cloned from Xenopus laevis, avian, rodent, and human species and is expressed in a wide range of cell types(13, 14, 19, 20) . In addition to activation of pp125 following stimulation of -integrins (11) and glycoprotein IIb/IIIa integrin(21) , it has been observed that pp125 is activated in signaling mediated via high affinity IgE receptors (22, 23) and neuropeptide receptors (24) and upon oncogenic transformation (16) in adherent cells. In cells expressing both pp125 and src, pp60formed a stable complex with pp125(25, 26) . Functional studies of pp125 protein in various systems showed that bradykinin stimulated tyrosine phosphorylation of pp125, paxillin, Ras GTPase-activating protein-associated p125, and src transformation-associated p130(27) . In addition, stable association of pp125 with phosphatidylinositol 3-kinase in NIH 3T3 mouse fibroblasts was observed(28) . pp125 expressed by nerve cell lines manifested increased tyrosine phosphorylation in response to Alzheimer's A peptide(24) . Recently, a novel pp125-related protein that is a substrate of tyrosine kinases in T and B lymphocytes was reported(29) .

Relatively little is known about the repertoire of signal transduction molecules in human megakaryocytes(30, 31) . Platelets, the progeny of megakaryocytes, contain pp125 that is phosphorylated on tyrosine following platelet activation(18, 32) . We have identified and characterized a novel intracytoplasmic kinase isolated from human megakaryocytic and brain cells with 48% identity (65% similarity) to pp125. We have also cloned the murine homolog of this cDNA. Given its homology to pp125, we have termed this new gene a related adhesion focal tyrosine kinase (RAFTK). Based on its molecular structure, its pattern of expression, and the induction of tyrosine phosphorylation of RAFTK proteins by thrombin in megakaryocytic cells, it is likely that RAFTK participates in signal transduction and may have a role in cell growth and differentiation.

EXPERIMENTAL PROCEDURES

Materials

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Cells

DNA Amplification and Cloning

Isolation and Characterization of cDNA Clones

A 340-bp probe was prepared from the 5`-end of one of the CMK cDNA clones (termed 2-1) and used to screen the human brain (hippocampus) cDNA library. Twelve clones were isolated, and two clones were sequenced on both strands. In addition, a 248-bp probe was prepared from the 5`-end of one of the clones (termed 4C), and the human hippocampus cDNA library was rescreened. Twelve clones were identified and isolated, and of these, one clone (termed 3B) was sequenced on both strands.

The mouse brain cDNA library (catalog No. ML1042b, CLONTECH, Palo Alto, CA) in gt11 vector was screened (5 10 recombinants/screening) using the 381-bp 5` KpnI fragment or the 764-bp ApaI 3`-fragment of human RAFTK cDNA as a probe, and the filters were hybridized and washed under high stringency conditions. Six clones were isolated. The DNA was isolated as described previously (38) , subcloned into pBSK, and thereafter sequenced. Nucleotide sequences were determined by the automated laser fluorescent DNA sequencer using Autoread (Pharmacia Biotech Inc.) and by manual sequencing using the Sequenase kit.

Chromosomal Localization of the Human RAFTK Gene

Backcross Mapping of the Mouse Raftk Gene

Recombinant Inbred (RI) Line Mapping of the Mouse Raftk Gene

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Northern Blot Analysis

PCR Blots

Figure 1: A, schematic representation and restriction enzyme map of the RAFTK cDNA. The various cDNA clones, obtained from the human hippocampus cDNA library (in ZAPII vector) and the CMK phorbol 12-myristate 13-acetate cDNA library (in gt10 vector), are shown as indicated. Restriction enzyme sites are indicated along the length of the cDNA. B, nucleotide and deduced amino acid sequences of the RAFTK cDNA clone representing the full-length cDNA. Nucleotide numbers are shown on the left. The amino acid numbers are shown on the right. The putative initiation codon at nucleotides 294-296 is shown in boldface type. The catalytic domain is boxed. The ATP-binding site is underlined, and the putative phosphorylation sites are encircled. The asterisk refers to the stop codon.

Protein Analysis

For metabolic labeling, 10 cells were labeled with 100 µCi of [S]methionine in 1 ml of Dulbecco's modified Eagle's medium minus methionine (Amersham Corp.) for 16 h. Immunoprecipitation of RAFTK protein from labeled cells with RAFTK antiserum or with normal rabbit serum was performed as described previously(31, 45) . For immunoprecipitation of Tyr(P) proteins, cold soluble extracts were first incubated with RAFTK antibodies (R-4250) overnight at 4 °C. The extracts were then incubated with protein G-Sepharose beads precoupled to goat anti-rabbit IgG for 1.5 h at 4 °C. Proteins were eluted from the beads by heating the samples at 100 °C for 5 min in SDS-polyacrylamide gel electrophoresis buffer. Proteins were separated by SDS-polyacrylamide gel electrophoresis, transferred, and immunoblotted with PY-20 (diluted 1:5000). The immunoreactive bands were visualized using the ECL system.

Antibodies

RESULTS

Isolation and Characterization of RAFTK cDNAs

Figure 2: Alignment of the predicted amino acid sequences (single-letter code) of mouse Raftk, human RAFTK, and the mouse pp125 gene translated product. Amino acid residues found to be conserved are boxed.

Figure 3: Comparison of the deduced amino acid sequence of RAFTK with those of m-pp125, Src, c-Fyn, Htk, and Fgfr. Gaps (indicated by dashes) were introduced to optimize the alignment. Amino acid residues found to be conserved are boxed.

Molecular Cloning of the Full-length Murine Raftk cDNA

Chromosomal Localization of the Human RAFTK Gene

Figure 4: Mapping of RAFTK in humans to chromosome 8 using human RAFTK cDNA. Shown are BamHI-digested genomic DNAs from hamster (h), human (H), and mouse (M) as well as 24 human/rodent somatic cell hybrids (labeled 1-22, X, and Y) probed with RAFTK cDNA. The human-specific RFLP is indicated with arrows and is seen in the human control lane and lane 8. A faint signal is observed in lane 20.

Chromosomal Localization of the Mouse Raftk Gene

Figure 5: Mapping of Raftk to mouse chromosome 14. A, BamHI restriction enzyme pattern for C57BL/6J (B) and M. spretus (S) genomic DNAs probed with the 1.4-kb human RAFTK cDNA. The molecular sizes of the fragments (in kilobase pairs) are indicated. B, haplotype analysis of chromosome 14 genetic markers in (C57BL/6J M. spretus)F M. spretus BSS-type backcross mice showing linkage and relative position of Raftk. Closed boxes indicate the inheritance of the C57BL/6J (B) allele, and open boxes indicate the inheritance of the M. spretus (S) allele from the (C57BL/6J M. spretus)F parent. Gene names and references to these loci can be found in GBASE. The first two columns indicate the number of backcross progeny with no recombinations. The following columns indicate recombinational events between adjacent loci (signified by a change from an open box to a closed box). The number of recombinants is listed below each column, and the recombination frequency (REC %) between adjacent loci is indicated.

The position of Raftk on mouse chromosome 14 was confirmed by determining the segregation of a SacI RFLP for Raftk DNAs from BxD RI lines. The SacI RFLP for Raftk was indicated by the presence of a 16.5-kb genomic DNA band in C57BL/6J or a 6.2-kb fragment in DBA/2J (Fig. 6A). These alleles were characterized for 26 DNAs from the BxD RI line (Fig. 6B). The strain distribution patterns of Raftk and the locus coding for gonadotropin-releasing hormone, Gnrh(50) , indicate close linkage between these two loci on chromosome 14 (Fig. 6B). Perfect concordance was observed with the BxD strain distribution pattern for the Gnrh locus, indicating linkage of <1-map unit distance from Raftk Gnrh(51) . These mapping data place Raftk distal to Nfl and are a contradiction to the backcross data. However, backcross data are not as accurate as RI data since backcross mice were derived from an interspecies cross.

Figure 6: Cosegregation of Raftk and Gnrh in BxD RI lines and localization to chromosome 14. A, SacI restriction enzyme pattern for C57BL/6J (B) and DBA/2J (D) genomic DNAs probed with the 1.4-kb human RAFTK cDNA. The molecular sizes of the fragments (in kilobase pairs) are indicated. B, strain distribution pattern for Raftk in the BxD RI lines. The RI line distribution pattern is compared with that of the Gnrh locus. Map units are indicated between Raftk and Gnrh, as are 95% confidence limits.

Expression of RAFTK in Tissues and Cell Lines

Northern blot analysis of RNA from human fetal heart, brain, lung, liver, and kidney revealed a weak single major species of mRNA of 4.5 kb in brain, and it appears to be expressed at low levels in lung and liver (Fig. 7A). Expression in human adult tissues was assessed by hybridization of the cDNA probe to a Northern blot of poly(A) RNA from heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas. While heart and skeletal muscle RNA samples were negative for RAFTK, a single mRNA was observed in all other tissues, with the highest levels expressed in brain (Fig. 7B). To further characterize the distribution of RAFTK expression in other human tissues, Northern blot analysis of spleen, thymus, prostate, testis, ovary, intestine, colon, and peripheral blood leukocytes revealed a high level of expression of RAFTK in thymus, spleen, and peripheral blood leukocytes (Fig. 7C). Northern blot analysis of different human brain regions (amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus, and thalamus) revealed that the highest level of expression of RAFTK was in the amygdala and hippocampus (Fig. 8). A lower level of expression was observed in the other brain regions, with the exception of the corpus callosum and substantia nigra, where there was no detectable signal. These results indicate that the brain has abundant expression of RAFTK, especially in the amygdala and hippocampus.

Figure 7: RAFTK expression. A, expression of RAFTK by Northern blot analysis in human fetal tissues; B, expression of RAFTK by Northern blot analysis in human adult tissues; C, expression of RAFTK by Northern blot analysis in various human tissues. The RNA blots were hybridized with a P-labeled RAFTK gene-specific probe, followed by hybridization with -actin (A and B) or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (C) as the control for uniform RNA loading. Skel. Musc., skeletal muscle; PBL, peripheral blood leukocytes.

Figure 8: Expression of RAFTK by Northern blot analysis in human brain regions. The RNA blot was hybridized as described in the legend of Fig. 6. Caud. Nucl., caudate nucleus; Corp. Callos., corpus callosum; Hippoc., hippocampus; Hypothal., hypothalamus; Subst. Nigra, substantia nigra; Subthal. Nucl., subthalamic nucleus; GAPDH, glyceraldehyde-3-phosphate dehydrogenase.

Expression of RAFTK was observed in several megakaryocytic cell lines such as CMK, Mo7e, HEL, and DAMI (data not shown). In addition, expression of RAFTK was detected in Ramos, FHS, and HeLa cells, but a low level of expression was detected in Jurkat, Hep3B, and CCL75 cells (data not shown). Using PCR techniques, expression of RAFTK was also found in primary bone marrow megakaryocytes, blood platelets, and CD34 marrow progenitor cells. Interestingly, it appears that the level of expression of RAFTK mRNA is similar to that of FAK in CD34 cells and is higher than that of FAK in bone marrow megakaryocytes. In platelets, the level of expression of RAFTK mRNA is lower than that of FAK, as observed by PCR under the same experimental conditions. It appears also that RAFTK mRNA expression in bone marrow megakaryocytes is higher than that in CD34 cells (Fig. 9). Taken together, these results indicate that RAFTK is abundantly expressed in brain and hematopoietic cells. The restricted expression observed in fetal versus adult tissues indicates that its expression is up-regulated during development.

Figure 9: Expression of RAFTK in hematopoietic cells. Shown is RAFTK expression by PCR in human CD34 marrow cells (lane 3), human bone marrow megakaryocytes (lane 4), and human platelets (lane 5). CD34 cells, platelets, and bone marrow megakaryocytes were processed as described under ``Experimental Procedures.'' The PCR products were electrophoresed on a 2% agarose gel and hybridized with gene-specific probes for RAFTK, FAK, and actin. Actin was used as an internal control in this set of experiments. PCR controls were as follows: lane 1, RNA alone; lane 2, primers alone.

Generation of Specific Antibodies for RAFTK and Detection of RAFTK Protein

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The specificity of this antiserum was examined by immunoprecipitation. The CMK cell line was metabolically labeled with [S]methionine, and extracts were immunoprecipitated with anti-RAFTK antiserum. A major protein species of 123 kDa was detected in CMK cells (Fig. 10A). A similar species was observed in other human megakaryocytic cell lines such as DAMI (data not shown). This band was not observed when normal rabbit serum or preimmune rabbit serum was used for immunoprecipitation. Incubation of R-4250 with 1 or 10 µg of the GST-RAFTK C terminus fusion protein abolished the appearance of the 123-kDa protein, while incubation with 10 µg of the GST-MATK (where MATK is megakaryocyte tyrosine kinase) SH2 domain fusion protein did not have any effects. These results indicate that R-4250 polyclonal antibodies specifically recognize RAFTK protein of 123 kDa in size. Furthermore, thrombin (1 unit/ml) stimulated a rapid increase in the amount of RAFTK protein immunoreactivity in anti-Tyr(P) immunoprecipitates (Fig. 10B). These results indicate that RAFTK is a protein-tyrosine kinase and that thrombin can induce its tyrosine phosphorylation.

Figure 10: The RAFTK protein. A, detection of RAFTK protein in vivo. CMK cells were metabolically labeled with 100 µCi of [S]methionine for 16 h, and the cell lysate was immunoprecipitated by normal rabbit serum (lane 1), preimmune rabbit (pre-R-4250) serum (lane 2), polyclonal antiserum for RAFTK (R-4250) (lane 3), or anti-RAFTK antiserum(4250) incubated with 1 µg (lane 4) or 10 µg (lane 5) of GST-RAFTK C terminus fusion protein or with 10 µg of GST-MATK SH2 domain fusion protein (31) as a control (lane 6). B, tyrosine phosphorylation of thrombin-stimulated CMK cells. CMK cells from whole cell lysates untreated (lane 1) or stimulated with thrombin (1 (lane 2) and 2 (lane 3) units/ml) for 5 min were immunoprecipitated with RAFTK polyclonal antiserum R-4250 and then immunoblotted with the same antibody (B) or immunoblotted with anti-Tyr(P) antibody PY-20 (C). Bands were visualized using the ECL system.

DISCUSSION

The method of PCR cloning has been successfully employed by many laboratories to identify novel members of the protein-tyrosine kinase family. Using this strategy, we have identified a novel intracytoplasmic tyrosine kinase in human megakaryocytic cells that we have termed RAFTK. Sequence analysis of RAFTK revealed 48% identity (65% similarity) to pp125, suggesting that RAFTK belongs to this subfamily of cytoplasmic tyrosine kinases. RAFTK does not appear to be the recently described FAKB protein(29) , also related to pp125, since the specific amino acid sequence used to make antisera that recognized FAKB protein is missing in the predicted amino acid sequence of RAFTK protein (Fig. 2). Furthermore, unlike FAKB, RAFTK protein did not form stable complexes with the T-cell antigen receptor/CD3-linked tyrosine kinase ZAP 70 in T-cells, indicating that RAFTK and FAKB are different proteins.

The chicken, human, and mouse focal adhesion kinases have been recently implicated as playing key roles in signal transduction pathways associated with extracellular adhesion molecules and with receptors for neuropeptide growth factors(14, 15, 52, 53) . Thus, based on its homology to pp125, one would expect RAFTK to participate in signaling pathways as well. The deduced 1009-amino acid sequence of RAFTK (with a calculated molecular mass of 120 kDa) contains a kinase domain and lacks a transmembrane region, myristylation sites, and SH2 and SH3 domains (Fig. 1B). To identify conserved regions within RAFTK between species that may have important functions, we have cloned the murine homolog of the human RAFTK cDNA. The sequence identity between the human RAFTK and murine Raftk cDNAs is 90% at the nucleotide level and 95.6% at the predicted amino acid level. In the kinase domain, 98.5% of the amino acids are identical (Fig. 2). Therefore, the RAFTK gene is highly conserved in human and rodent, again suggesting an important role in cell signaling functions. RAFTK has an insertion of an additional 4 amino acids between positions 76 and 81 (Gly-Arg-Ile-Gly) compared with chicken, murine, and human pp125 sequences (Fig. 2)(13, 14, 19) . Amino acids corresponding to positions 292-320 of human pp125 and amino acids corresponding to positions 850-864 and 901-926 of chicken pp125 are absent in the predicted RAFTK protein. Interestingly, like chicken pp125, the C terminus region of human RAFTK and mouse Raftk contains a proline-rich stretch (residues 690-767). It has been shown that proteins containing proline-rich peptide motifs (such as Shc, p62, and ribonucleoprotein K) could serve as SH3 domain ligands and that the binding of these proteins to the Src SH3 domain was inhibited with a proline-rich peptide ligand(54) . Furthermore, the predicted RAFTK protein, like the pp125 protein, displays several unique features among the known tyrosine kinases. The primary sequence of RAFTK does not contain a signal peptide or a membrane-spanning region, and the protein is therefore presumed to be located in the cytoplasm. RAFTK lacks SH2 and SH3 domains, which are structural elements involved in protein-protein interactions(2, 47, 55, 56, 57) , and does not exhibit significant homology to any known protein-tyrosine kinase beyond pp125 outside of the catalytic domain ( Fig. 2and Fig. 3). Lack of SH2 and SH3 domains suggests that other regions within RAFTK protein are important for protein interaction and targeting. In the case of the pp125 protein, it has been demonstrated by structural-functional analysis that 159 amino acids within the C terminus are essential as a ``focal adhesion targeting'' sequence(58) . The homology between RAFTK and pp125 within this region is 52%. The overall structure of RAFTK is characteristic of the pp125 gene, with the catalytic domain flanked by large N- and C-terminal domains (Fig. 2). It has recently been reported that deletions of the N- or C-terminal noncatalytic domain of pp125 including Tyr did not abolish the kinase activity of pp125(59) . Moreover, there is conservation of several tyrosine residues between RAFTK and pp125 ( Fig. 2and Fig. 3), including Tyr, which has been shown to be the major site of tyrosine phosphorylation in pp125 protein(25) .

RAFTK-specific mRNA expression was observed in human fetal tissues, being most abundant in brain (predominantly in the amygdala and hippocampus regions), and appeared to be developmentally up-regulated as demonstrated in the pattern of adult tissue expression ( Fig. 7(A-C) and 8). Within the hematopoietic system, in addition to peripheral blood leukocytes, a high level of specific mRNA expression of RAFTK was detected in B-cells and various megakaryocytic cell lines (data not shown). By using PCR, the specific mRNA expression of RAFTK was also detected in CD34 primary bone marrow progenitor cells, primary bone marrow megakaryocytes, and platelets (Fig. 9).

RAFTK is phosphorylated after thrombin treatment of CMK cells. Interestingly, FAK protein was also found phosphorylated on tyrosine after thrombin or collagen treatment of platelets(18) . There is considerable homology in the thrombin receptors and considerable signal similarities in transduction mechanisms between platelets and megakaryocytes(60) . Furthermore, bone marrow megakaryocytes in liquid culture stimulated with thrombin for 5 min revealed dramatic morphological changes reminiscent of those found in platelets, including shape change and organelle centralization that involved immature as well as mature cells(61) . Megakaryocytes were also able to secrete -granule proteins in the dilated cisternae of the demarcation membrane system(61) .

The human RAFTK gene was found on chromosome 8 using DNAs from the somatic cell hybrid lines (Fig. 4). The signal observed in cell line 20 in mapping panel 2 suggested that a fragment of chromosome 8 is in the chromosome 20 cell line. Indeed, although cell line 20 contained the human NEFL gene, there was no evidence of chromosome 20 or a fragment of chromosome 20 in cell line 8 (Coriel Cell Institute for Medical Research). Indeed, the localization of RAFTK to chromosome 8 was confirmed using mapping panel 1. The human NEFL gene has been localized to chromosome 8p21 (62) . Nfl, the murine homolog of human NEFL, has been mapped to mouse chromosome 14 and is within 3 cM of the Gnrh locus (GBASE). The close linkage of the mouse Raftk gene to Nfl (whose NEFL homolog is on human chromosome 8p21) suggested that the human RAFTK gene may be mapped to chromosome 8 based on homology between human and mouse chromosomes(62) . Therefore, we predict that the human RAFTK gene will be localized to chromosome 8p21. We have mapped the mouse Raftk gene to chromosome 14 using a (C57BL/6J M. spretus)F M. spretus backcross. The position of mouse Raftk was confirmed by RI line mapping using the BxD RI lines. The Raftk gene was also shown to be closely linked to Gnrh, whose human homolog (LHRH (luteinizing hormone-releasing hormone)) has been mapped to human chromosome 8p21-11.2(42) .

There has been considerable interest in the role of pp125 in signaling pathways in a variety of normal and transformed cells in response to different soluble and cell-surface stimuli. Future studies will aim to gain insights into the function of RAFTK in these signal transduction pathways, particularly distinguishing a role for RAFTK versus pp125 in these systems.

FOOTNOTES

*

This work was supported in part by National Institutes of Health Grants HL51456 and HL46668. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This paper is dedicated to Ronald Ansin for his friendship and support for our research program.

§

To whom correspondence should be addressed: Div. of Hematology/Oncology, Deaconess Hospital, One Deaconess Rd., Boston, MA 02215. Tel.: 617-632-0524; Fax: 617-424-6237.

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The abbreviations used are: PCR, polymerase chain reaction; bp, base pair(s); kb, kilobase pair(s); RFLP, restriction fragment length polymorphism; RI, recombinant inbred; FAK, focal adhesion kinase; GST, glutathione S-transferase.

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L. J. Maltais, D. P. Doolittle, A. L. Hillyard, J. N. Guidi, M. T. Davisson, and T. H. Roderick(1993) GBASE, the genomic data base of the mouse maintained at The Jackson Laboratory.

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J. Li, personal communication.

ACKNOWLEDGEMENTS

REFERENCES

1. Ullrich, A., and Schlessinger, J. (1990) Cell 61, 203-212 [CrossRef][Medline] [Order article via Infotrieve]
2. Pawson, T., and Gish, G. D. (1992) Cell 71, 359-362 [CrossRef][Medline] [Order article via Infotrieve]
3. Fantl, W. J., Johnson, D. E., and Williams, L. T. (1993) Annu. Rev. Biochem. 62, 453-481 [Medline] [Order article via Infotrieve]
4. Cantley, L. C., Auger, K. R., Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R., and Soltoff, S. (1991) Cell 64, 281-302 [CrossRef][Medline] [Order article via Infotrieve]
5. Shattil, S. J., and Brugge, J. S. (1991) Curr. Opin. Cell Biol. 3, 869-879 [CrossRef][Medline] [Order article via Infotrieve]
6. Weiss, A. (1993) Cell 73, 209-212 [CrossRef][Medline] [Order article via Infotrieve]
7. Hynes, R. O. (1992) Cell 69, 11-25 [CrossRef][Medline] [Order article via Infotrieve]
8. Juliano, R. L., and Haskill, S. (1993) J. Cell Biol. 120, 577-585 [Free Full Text]
9. Schwartz, M. A. (1992) Trends Cell Biol. 2, 304-308 [CrossRef][Medline] [Order article via Infotrieve]
10. Guan, J.-L., Trevithick, J. E., and Hynes, R. O. (1991) Cell Regul. 2, 951-964 [Medline] [Order article via Infotrieve]
11. Kornberg, L. J., Earp, H. S., Turner, C. E., Prockop, C., and Juliano, R. L. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 8392-8396 [Abstract/Free Full Text]
12. Hanks, S. K., Calalb, M. B., Harper, M. C., and Patel, S. K. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 8487-8489 [Abstract/Free Full Text]
13. Schaller, M. D., Borgman, C. A., Cobb, B. S., Vines, R. R., Reynolds, A. B., and Parsons, J. T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5192-5196 [Abstract/Free Full Text]
14. Schaller, M. D., and Parsons, J. T. (1993) Trends Cell Biol. 3, 258-262 [CrossRef][Medline] [Order article via Infotrieve]
15. Zachary, I., and Rozengurt, E. (1992) Cell 71, 891-894 [CrossRef][Medline] [Order article via Infotrieve]
16. Guan, J.-L., and Shalloway, D. (1992) Nature 358, 690-692 [CrossRef][Medline] [Order article via Infotrieve]
17. Kornberg, L., Earp, H. S., Parsons, J. T., Schaller, M. D., and Juliano, R. L. (1992) J. Biol. Chem. 267, 23439-23442 [Abstract/Free Full Text]
18. Lipfert, L., Haimovich, B., Schaller, M. D., Cobb, B. S., Parsons, J. T., and Brugge, J. S. (1992) J. Cell Biol. 119, 905-912 [Abstract/Free Full Text]
19. Clark, E. A., and Brugge, J. S. (1995) Science 268, 233-239 [Abstract/Free Full Text]
20. Devor, B. B., Zhang, X., Patel, S. K., Polte, T. R., and Hanks, S. K. (1993) Biochem. Biophys. Res. Commun. 190, 1084-1089 [CrossRef][Medline] [Order article via Infotrieve]
21. Ferrell, J. E., and Martin, G. S. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 2234-2238 [Abstract/Free Full Text]
22. Hamawy, M. M., Mergenhagen, S. E., and Siraganian, R. P. (1993) J. Biol. Chem. 268, 6851-6854 [Abstract/Free Full Text]
23. Hamawy, M. M., Swaim, W. D., Minoguchi, K., de Feijter, A. W., Mergenhagen, S. E., and Siraganian, R. P. (1994) J. Immunol. 153, 4655-4662 [Abstract]
24. Zhang, C., Lambert, M. P., Bunch, C., Barber, K., Wade, W. S., Krafft, G. A., and Klein, W. L. (1994) J. Biol. Chem. 269, 25247-25250 [Abstract/Free Full Text]
25. Schaller, M. D., Hildebrand, J. D., Shannon, J. D., Fox, J. W., Vines, R. R., and Parsons, J. T. (1994) Mol. Cell. Biol. 14, 1680-1688 [Abstract/Free Full Text]
26. Kaplan, K. B., Bibbins, K. B., Swedlow, J. R., Arnaud, M., Morgan, D. O., and Varmus, H. E. (1994) EMBO J. 13, 4745-4756 [Medline] [Order article via Infotrieve]
27. Leeb-Lundberg, L. M., Song, X.-H., and Mathis, S. A. (1994) J. Biol. Chem. 269, 24328-24334 [Abstract/Free Full Text]
28. Chen, H.-C., and Guan, J.-L. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10148-10152 [Abstract/Free Full Text]
29. Kanner, S. B., Aruffo, A., and Chan, P.-Y. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10484-10487 [Abstract/Free Full Text]
30. Avraham, H. (1993) Stem Cells 11, 499-510 [Abstract]
31. Bennett, B. D., Cowley, S., Jiang, S., London, R., Deng, B., Grabarek, J., Groopman, J. E., Goeddel, D. V., and Avraham, H. (1994) J. Biol. Chem. 269, 1068-1074 [Abstract/Free Full Text]
32. Shattil, S. J., Haimovich, B., Cunningham, M., Lipfert, L., Parsons, J. T., Ginsberg, M. H., and Brugge, J. S. (1994) J. Biol. Chem. 269, 14738-14745 [Abstract/Free Full Text]
33. Tanaka, H., Ishida, Y., Kaneko, T., and Matsumoto, N. S. (1989) Br. J. Haematol. 73, 18-22 [Medline] [Order article via Infotrieve]
34. Avraham, H., Scadden, D. T., Chi, S., Broudy, V., Zsebo, K., and Groopman, J. E. (1992) Blood 80, 1679-1684 [Abstract/Free Full Text]
35. Sato, T., Fuse, A., Eguchi, M., Hayashi, Y., Sugita, K., Nakazawa, S., Minato, K., Shima, Y., Komori, I., Sunami, S., Okimoto, Y., and Nakajima, H. (1987) Exp. Hematol. (N. Y.) 15, 495-502
36. Avraham, H., Vannier, E., Cowley, S., Jiang, S., Chi, S., Dinarello, C. A., Zsebo, K. M., and Groopman, J. E. (1992) Blood 79, 365-371 [Abstract/Free Full Text]
37. Avraham, H., Vannier, E., Chi, S. Y., Dinarello, C. A., and Groopman, J. E. (1992) Int. J. Cell Cloning 10, 70-75 [Abstract]
38. Maniatis, T., Fritsch, E. F., and Sambrook, J. (1992) Molecular Cloning: A Laboratory Manual , Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
39. Wilks, A. F. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 1603-1607 [Abstract/Free Full Text]
40. Rowe, L. B., Nadeau, J. H., Turner, R., Frankel, W. N., Letts, V. A., Eppig, J. T., Ko, M. S. H., Thurston, S. J., and Birkenmeier, E. H. (1994) Mamm. Genome 5, 253-274 [CrossRef][Medline] [Order article via Infotrieve]
41. White, R. A., Peters, L. L., Adkison, L. R., Korsgren, C., Cohen, C. M., and Lux, S. E. (1992) Nature Genetics 2, 80-83 [CrossRef][Medline] [Order article via Infotrieve]
42. Yang-Feng, T. L., Seeburg, P. H., and Francke, U. (1986) Somatic Cell. Mol. Genet. 12, 95-100 [CrossRef][Medline] [Order article via Infotrieve]
43. Andre, E., and Becker-Andre, M. (1993) Biochem. Biophys. Res. Commun. 190, 140-147 [CrossRef][Medline] [Order article via Infotrieve]
44. Laemmli, U. K. (1970) Nature 227, 680-685 [CrossRef][Medline] [Order article via Infotrieve]
45. Yarden, Y., Kuang, W., Yang-Feng, T., Coussens, L., Munemitsu, S., Dull, T. J., Chen, E., Schlessinger, J., Francke, U., and Ullrich, A. (1987) EMBO J. 6, 3341-3351 [Medline] [Order article via Infotrieve]
46. Konopka, J. B., and Witte, O. N. (1985) Mol. Cell. Biol. 5, 3116-3123 [Abstract/Free Full Text]
47. Konopka, J. B., Davis, R. L., Watanabe, S. M., Ponticelli, A. S., Schiff-Maker, L., Rosenberg, N., and Witte, O. N. (1984) J. Virol. 51, 223-232 [Abstract/Free Full Text]
48. Dymecki, S. M., Zwollo, P., Zeller, K., Kuhajda, F. P., and Desiderio, S. V. (1992) J. Biol. Chem. 267, 4815-4823 [Abstract/Free Full Text]
49. Bennett, B. D., Bennett, G. L., Vitangcol, R. V., Jewett, J. R. S., Burnier, J., Henzel, W., and Lowe, D. G. (1991) J. Biol. Chem. 266, 23060-23067 [Abstract/Free Full Text]
50. Hearne, C. M., McAleer, M. A., Love, J., Aitman, T. J., Cornall, R. J., Ghosh, S., Knight, A., Prins, J.-B., and Todd, J. A. (1991) Mamm. Genome 1, 273-282 [CrossRef][Medline] [Order article via Infotrieve]
51. Silver, J. (1985) J. Hered. 76, 436-440 [Abstract/Free Full Text]
52. Leeb-Lundberg, L. M., and Song, X.-H. (1991) J. Biol. Chem. 266, 7746-7749 [Abstract/Free Full Text]
53. Zachary, I., Sinnett-Smith, J., and Rozengurt, E. (1992) J. Biol. Chem. 267, 19031-19034 [Abstract/Free Full Text]
54. Weng, Z., Thomas, S. M., Rickles, R. J., Taylor, J. A., Brauer, A. W., Seidel-Dugan, C., Michael, W. M., Dreyfuss, G., and Brugge, J. S. (1994) Mol. Cell. Biol. 14, 4509-4521 [Abstract/Free Full Text]
55. Waksman, G., Kominos, D., Robertson, S. C., Pant, N., Baltimore, D., Birge, R. B., Cowburn, D., Hanafusa, H., Mayer, B. J., Overduin, M., Resh, M. D., Rios, C. B., Silverman, L., and Kuriyan, J. (1992) Nature 358, 646-653 [CrossRef][Medline] [Order article via Infotrieve]
56. Taylor, S. J., and Shalloway, D. (1993) Current Opin. Genet. & Dev. 3, 26-34
57. Yu, H., Rosen, M. K., Shin, T. B., Seidel-Dugan, C., Brugge, J. S., and Schreiber, S. L. (1992) Science 258, 1665-1668 [Abstract/Free Full Text]
58. Hildebrand, J. D., Schaller, M. D., and Parsons, J. T. (1993) J. Cell Biol. 123, 993-1005 [Abstract/Free Full Text]
59. Chan, P.-Y., Kanner, S. B., Whitney, G., and Aruffo, A. (1994) J. Biol. Chem. 269, 20567-20574 [Abstract/Free Full Text]
60. Vittet, D., and Chevillard, C. (1993) Blood Coagul. & Fibrinolysis 4, 759-768
61. Cramer, E. M., Masse, J. M., Caen, J. P., Garcia, I., Breton-Gorius, J., Debili, N., and Vainchenker, W. (1993) Am. J. Pathol. 143, 1498-1508 [Abstract]
62. Hurst, J., Flavell, D., Julien, J.-P., Meijer, D., Mushynski, W., and Grosveld, F. (1987) Cytogenet. Cell Genet. 45, 30-32 [Medline] [Order article via Infotrieve]

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				J. Fujimoto, K. Sawamoto, M. Okabe, Y. Takagi, T. Tezuka, S. Yoshikawa, H. Ryo, H. Okano, and T. Yamamoto Cloning and Characterization of Dfak56, a Homolog of Focal Adhesion Kinase, in Drosophila melanogaster J. Biol. Chem., October 8, 1999; 274(41): 29196 - 29201. [Abstract] [Full Text] [PDF]

				J. A. Hartigan and G. V. W. Johnson Transient Increases in Intracellular Calcium Result in Prolonged Site-selective Increases in Tau Phosphorylation through a Glycogen Synthase Kinase 3beta -dependent Pathway J. Biol. Chem., July 23, 1999; 274(30): 21395 - 21401. [Abstract] [Full Text] [PDF]

				J. D. Owen, P. J. Ruest, D. W. Fry, and S. K. Hanks Induced Focal Adhesion Kinase (FAK) Expression in FAK-Null Cells Enhances Cell Spreading and Migration Requiring Both Auto- and Activation Loop Phosphorylation Sites and Inhibits Adhesion-Dependent Tyrosine Phosphorylation of Pyk2 Mol. Cell. Biol., July 1, 1999; 19(7): 4806 - 4818. [Abstract] [Full Text] [PDF]

				J. L. Rodríguez-Fernández, M. Gómez, A. Luque, N. Hogg, F. Sánchez-Madrid, and C. Cabañas The Interaction of Activated Integrin Lymphocyte Function-associated Antigen 1 with Ligand Intercellular Adhesion Molecule 1 Induces Activation and Redistribution of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 in T Lymphocytes Mol. Biol. Cell, June 1, 1999; 10(6): 1891 - 1907. [Abstract] [Full Text]

				A. Blaukat, I. Ivankovic-Dikic, E. Gronroos, F. Dolfi, G. Tokiwa, K. Vuori, and I. Dikic Adaptor Proteins Grb2 and Crk Couple Pyk2 with Activation of Specific Mitogen-activated Protein Kinase Cascades J. Biol. Chem., May 21, 1999; 274(21): 14893 - 14901. [Abstract] [Full Text] [PDF]

				P. Pandey, S. Avraham, S. Kumar, A. Nakazawa, A. Place, L. Ghanem, A. Rana, V. Kumar, P. K. Majumder, H. Avraham, et al. Activation of p38 Mitogen-activated Protein Kinase by PYK2/Related Adhesion Focal Tyrosine Kinase-dependent Mechanism J. Biol. Chem., April 9, 1999; 274(15): 10140 - 10144. [Abstract] [Full Text] [PDF]

				P. Pandey, S. Avraham, A. Place, V. Kumar, P. K. Majumder, K. Cheng, A. Nakazawa, S. Saxena, and S. Kharbanda Bcl-xL Blocks Activation of Related Adhesion Focal Tyrosine Kinase/Proline-rich Tyrosine Kinase 2 and Stress-activated Protein Kinase/c-Jun N-terminal Protein Kinase in the Cellular Response to Methylmethane Sulfonate J. Biol. Chem., March 26, 1999; 274(13): 8618 - 8623. [Abstract] [Full Text] [PDF]

				X. Li, R. C. Dy, W. G. Cance, L. M. Graves, and H. S. Earp Interactions between Two Cytoskeleton-associated Tyrosine Kinases: Calcium-dependent Tyrosine Kinase and Focal Adhesion Tyrosine Kinase J. Biol. Chem., March 26, 1999; 274(13): 8917 - 8924. [Abstract] [Full Text] [PDF]

				M. Tsuchida, S. J. Knechtle, and M. M. Hamawy CD28 Ligation Induces Tyrosine Phosphorylation of Pyk2 but Not Fak in Jurkat T Cells J. Biol. Chem., March 5, 1999; 274(10): 6735 - 6740. [Abstract] [Full Text] [PDF]

				S. Lev, J. Hernandez, R. Martinez, A. Chen, G. Plowman, and J. Schlessinger Identification of a Novel Family of Targets of PYK2 Related to Drosophila Retinal Degeneration B (rdgB) Protein Mol. Cell. Biol., March 1, 1999; 19(3): 2278 - 2288. [Abstract] [Full Text] [PDF]

				P. T. Lakkakorpi, I. Nakamura, R. M. Nagy, J. T. Parsons, G. A. Rodan, and L. T. Duong Stable Association of PYK2 and p130Cas in Osteoclasts and Their Co-localization in the Sealing Zone J. Biol. Chem., February 19, 1999; 274(8): 4900 - 4907. [Abstract] [Full Text] [PDF]

				S. Eguchi, H. Iwasaki, T. Inagami, K. Numaguchi, T. Yamakawa, E. D. Motley, K. M. Owada, F. Marumo, and Y. Hirata Involvement of PYK2 in Angiotensin II Signaling of Vascular Smooth Muscle Cells Hypertension, January 1, 1999; 33(1): 201 - 206. [Abstract] [Full Text] [PDF]

				A. Sabri, G. Govindarajan, T. M. Griffin, K. L. Byron, A. M. Samarel, and P. A. Lucchesi Calcium- and Protein Kinase C–Dependent Activation of the Tyrosine Kinase PYK2 by Angiotensin II in Vascular Smooth Muscle Circ. Res., October 19, 1998; 83(8): 841 - 851. [Abstract] [Full Text] [PDF]

				U. Widegren, X. J. Jiang, A. Krook, A. V. Chibalin, M. Björnholm, M. Tally, R. A. Roth, J. Henriksson, H. Wallberg-henriksson, and J. R. Zierath Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle FASEB J, October 1, 1998; 12(13): 1379 - 1389. [Abstract] [Full Text]

				S. Murasawa, Y. Mori, Y. Nozawa, H. Masaki, K. Maruyama, Y. Tsutsumi, Y. Moriguchi, Y. Shibasaki, Y. Tanaka, T. Iwasaka, et al. Role of Calcium-Sensitive Tyrosine Kinase Pyk2/CAKß/RAFTK in Angiotensin II–Induced Ras/ERK Signaling Hypertension, October 1, 1998; 32(4): 668 - 675. [Abstract] [Full Text] [PDF]

				M. Nagao, J. Yamauchi, Y. Kaziro, and H. Itoh Involvement of Protein Kinase C and Src Family Tyrosine Kinase in Galpha q/11-induced Activation of c-Jun N-terminal Kinase and p38 Mitogen-activated Protein Kinase J. Biol. Chem., September 4, 1998; 273(36): 22892 - 22898. [Abstract] [Full Text] [PDF]

				R. K. Ganju, S. A. Brubaker, J. Meyer, P. Dutt, Y. Yang, S. Qin, W. Newman, and J. E. Groopman The alpha -Chemokine, Stromal Cell-derived Factor-1alpha , Binds to the Transmembrane G-protein-coupled CXCR-4 Receptor and Activates Multiple Signal Transduction Pathways J. Biol. Chem., September 4, 1998; 273(36): 23169 - 23175. [Abstract] [Full Text] [PDF]

				Z. Zhang, H. Avraham, and D. M. Cohen Urea and NaCl differentially regulate FAK and RAFTK/PYK2 in mIMCD3 renal medullary cells Am J Physiol Renal Physiol, September 1, 1998; 275(3): F447 - F451. [Abstract] [Full Text] [PDF]

				D.-H. Yu, C.-K. Qu, O. Henegariu, X. Lu, and G.-S. Feng Protein-tyrosine Phosphatase Shp-2 Regulates Cell Spreading, Migration, and Focal Adhesion J. Biol. Chem., August 14, 1998; 273(33): 21125 - 21131. [Abstract] [Full Text] [PDF]

				R. K. Ganju, N. Munshi, B. C. Nair, Z.-Y. Liu, P. Gill, and J. E. Groopman Human Immunodeficiency Virus Tat Modulates the Flk-1/KDR Receptor, Mitogen-Activated Protein Kinases, and Components of Focal Adhesion in Kaposi's Sarcoma Cells J. Virol., July 1, 1998; 72(7): 6131 - 6137. [Abstract] [Full Text] [PDF]

				J. Brockdorff, S. B. Kanner, M. Nielsen, N. Borregaard, C. Geisler, A. Svejgaard, and N. Odum Interleukin-2 induces beta 2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB) PNAS, June 9, 1998; 95(12): 6959 - 6964. [Abstract] [Full Text] [PDF]

				I. Dikic, I. Dikic, and J. Schlessinger Identification of a New Pyk2 Isoform Implicated in Chemokine and Antigen Receptor Signaling J. Biol. Chem., June 5, 1998; 273(23): 14301 - 14308. [Abstract] [Full Text] [PDF]

				A. E. Aplin, A. Howe, S. K. Alahari, and R. L. Juliano Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins Pharmacol. Rev., June 1, 1998; 50(2): 197 - 264. [Abstract] [Full Text] [PDF]

				J. S. Elmendorf, D. Chen, and J. E. Pessin Guanosine 5'-O-(3-Thiotriphosphate) (GTPgamma S) Stimulation of GLUT4 Translocation is Tyrosine Kinase-dependent J. Biol. Chem., May 22, 1998; 273(21): 13289 - 13296. [Abstract] [Full Text] [PDF]

				W. C. Hatch, R. K. Ganju, D. Hiregowdara, S. Avraham, and J. E. Groopman The Related Adhesion Focal Tyrosine Kinase (RAFTK) Is Tyrosine Phosphorylated and Participates in Colony-Stimulating Factor-1/Macrophage Colony-Stimulating Factor Signaling in Monocyte-Macrophages Blood, May 15, 1998; 91(10): 3967 - 3973. [Abstract] [Full Text] [PDF]

				B. P. Lipsky, C. R. Beals, and D. E. Staunton Leupaxin Is a Novel LIM Domain Protein That Forms a Complex with PYK2 J. Biol. Chem., May 8, 1998; 273(19): 11709 - 11713. [Abstract] [Full Text] [PDF]

				T.-A. Kim, J. Lim, S. Ota, S. Raja, R. Rogers, B. Rivnay, H. Avraham, and S. Avraham NRP/B, a Novel Nuclear Matrix Protein, Associates With p110RB and Is Involved in Neuronal Differentiation J. Cell Biol., May 4, 1998; 141(3): 553 - 566. [Abstract] [Full Text] [PDF]

				M. Jeschke, G. J. R. Standke, and M. Susa Fluoroaluminate Induces Activation and Association of Src and Pyk2 Tyrosine Kinases in Osteoblastic MC3T3-E1 Cells J. Biol. Chem., May 1, 1998; 273(18): 11354 - 11361. [Abstract] [Full Text] [PDF]

				J. S. Felsch, T. G. Cachero, and E. G. Peralta Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine receptor PNAS, April 28, 1998; 95(9): 5051 - 5056. [Abstract] [Full Text] [PDF]

				X. Li, D. Hunter, J. Morris, J. S. Haskill, and H. S. Earp A Calcium-dependent Tyrosine Kinase Splice Variant in Human Monocytes. ACTIVATION BY A TWO-STAGE PROCESS INVOLVING ADHERENCE AND A SUBSEQUENT INTRACELLULAR SIGNAL J. Biol. Chem., April 17, 1998; 273(16): 9361 - 9364. [Abstract] [Full Text] [PDF]

				S. Eguchi, K. Numaguchi, H. Iwasaki, T. Matsumoto, T. Yamakawa, H. Utsunomiya, E. D. Motley, H. Kawakatsu, K. M. Owada, Y. Hirata, et al. Calcium-dependent Epidermal Growth Factor Receptor Transactivation Mediates the Angiotensin II-induced Mitogen-activated Protein Kinase Activation in Vascular Smooth Muscle Cells J. Biol. Chem., April 10, 1998; 273(15): 8890 - 8896. [Abstract] [Full Text] [PDF]

				T. Miyazaki, A. Takaoka, L. Nogueira, I. Dikic, H. Fujii, S. Tsujino, Y. Mitani, M. Maeda, J. Schlessinger, and T. Taniguchi Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway Genes & Dev., March 15, 1998; 12(6): 770 - 775. [Abstract] [Full Text]

				R. K. Ganju, P. Dutt, L. Wu, W. Newman, H. Avraham, S. Avraham, and J. E. Groopman beta -Chemokine Receptor CCR5 Signals Via the Novel Tyrosine Kinase RAFTK Blood, February 1, 1998; 91(3): 791 - 797. [Abstract] [Full Text] [PDF]

				S. P. Soltoff, H. Avraham, S. Avraham, and L. C. Cantley Activation of P2Y2 Receptors by UTP and ATP Stimulates Mitogen-activated Kinase Activity through a Pathway That Involves Related Adhesion Focal Tyrosine Kinase and Protein Kinase C J. Biol. Chem., January 30, 1998; 273(5): 2653 - 2660. [Abstract] [Full Text] [PDF]

				C. Zheng, Z. Xing, Z. C. Bian, C. Guo, A. Akbay, L. Warner, and J.-L. Guan Differential Regulation of Pyk2 and Focal Adhesion Kinase (FAK). THE C-TERMINAL DOMAIN OF FAK CONFERS RESPONSE TO CELL ADHESION J. Biol. Chem., January 23, 1998; 273(4): 2384 - 2389. [Abstract] [Full Text] [PDF]

				A. E. Brinson, T. Harding, P. A. Diliberto, Y. He, X. Li, D. Hunter, B. Herman, H. S. Earp, and L. M. Graves Regulation of a Calcium-dependent Tyrosine Kinase in Vascular Smooth Muscle Cells by Angiotensin II and Platelet-derived Growth Factor. DEPENDENCE ON CALCIUM AND THE ACTIN CYTOSKELETON J. Biol. Chem., January 16, 1998; 273(3): 1711 - 1718. [Abstract] [Full Text] [PDF]

				M. Matsuya, H. Sasaki, H. Aoto, T. Mitaka, K. Nagura, T. Ohba, M. Ishino, S. Takahashi, R. Suzuki, and T. Sasaki Cell Adhesion Kinase beta  Forms a Complex with a New Member, Hic-5, of Proteins Localized at Focal Adhesions J. Biol. Chem., January 9, 1998; 273(2): 1003 - 1014. [Abstract] [Full Text] [PDF]

				H. Okazaki, J. Zhang, M. M. Hamawy, and R. P. Siraganian Activation of Protein-tyrosine Kinase Pyk2 Is Downstream of Syk in Fcepsilon RI Signaling J. Biol. Chem., December 19, 1997; 272(51): 32443 - 32447. [Abstract] [Full Text] [PDF]

				K. I.-P. J. Hidari, A. S. Weyrich, G. A. Zimmerman, and R. P. McEver Engagement of P-selectin Glycoprotein Ligand-1 Enhances Tyrosine Phosphorylation and Activates Mitogen-activated Protein Kinases in Human Neutrophils J. Biol. Chem., November 7, 1997; 272(45): 28750 - 28756. [Abstract] [Full Text] [PDF]

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