We have isolated a cDNA encoding a novel human intracytoplasmic tyrosine kinase, termed RAFTK (for a related adhesion focal tyrosine kinase). In addition, we have cloned and characterized the murine homolog of the human RAFTK cDNA. Comparison of the deduced amino acid sequences of human RAFTK and murine Raftk cDNAs revealed 95% homology, indicating that RAFTK is highly conserved between these species. The RAFTK cDNA clone, encoding a polypeptide of 1009 amino acids, has closest homology (48% identity, 65% similarity) to the focal adhesion kinase (pp125). Comparison of the deduced amino acid sequences also indicates that RAFTK, like pp125, lacks a transmembrane region, myristylation sites, and SH2 and SH3 domains. In addition, like pp125, RAFTK contains a kinase domain flanked by large N-terminal (426 residues) and C-terminal (331 residues) domains, and the C-terminal region contains a predicted proline-rich stretch of residues. In fetal tissues, RAFTK expression was abundant in brain, and low levels were observed in lung and liver. In adult tissues, it was less restricted, indicating that RAFTK expression is developmentally up-regulated. Expression of RAFTK was also observed in human CD34 marrow cells, primary bone marrow megakaryocytes, platelets, and various areas of brain. The human RAFTK gene was assigned to human chromosome 8 using genomic DNAs from human/rodent somatic cell hybrid lines. The mouse Raftk gene was mapped to chromosome 14, closely linked to gonadotropin-releasing hormone. Using specific antibodies for RAFTK, a 123-kDa protein from the human megakaryocytic CMK cell line was immunoprecipitated. Treatment of the megakaryocytic CMK cells with thrombin caused a rapid induction of tyrosine phosphorylation of RAFTK protein. The structural features of RAFTK suggest that it is a member of the focal adhesion kinase gene family and may participate in signal transduction in human megakaryocytes and brain as well as in other cell types.

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				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]