HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 36, 37651-37661, September 3, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/36/37651    most recent M311985200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Humphries, L. A. Articles by Rawlings, D. J. Search for Related Content PubMed PubMed Citation Articles by Humphries, L. A. Articles by Rawlings, D. J. Social Bookmarking                      What's this?

Tec Kinases Mediate Sustained Calcium Influx via Site-specific Tyrosine Phosphorylation of the Phospholipase C Src Homology 2-Src Homology 3 Linker^*

Lisa A. Humphries, Carol Dangelmaier, Karen Sommer¶, Kevin Kipp¶, Roberta M. Kato¶, Natasha Griffith||, Irene Bakman**, Christoph W. Turk, James L. Daniel, and David J. Rawlings¶¶¶

From the Molecular Biology Institute and Departments of ^||Microbiology and Immunology and ^**Chemical Engineering, UCLA, Los Angeles, California 90095, the Departments of Immunology and ^¶Pediatrics, University of Washington School of Medicine, Seattle, Washington 98195, the Department of Pharmacology and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, and Max Plank Institute of Psychiatry, Molecular, Cellular, and Clinical Proteomics, Munich, Germany 80804

Tyrosine phosphorylation of phospholipase C2 (PLC2) is a crucial activation switch that initiates and maintains intracellular calcium mobilization in response to B cell antigen receptor (BCR) engagement. Although members from three distinct families of non-receptor tyrosine kinases can phosphorylate PLC in vitro, the specific kinase(s) controlling BCR-dependent PLC activation in vivo remains unknown. Bruton's tyrosine kinase (Btk)-deficient human B cells exhibit diminished inositol 1,4,5-trisphosphate production and calcium signaling despite a normal inducible level of total PLC2 tyrosine phosphorylation. This suggested that Btk might modify a critical subset of residues essential for PLC2 activity. To evaluate this hypothesis, we generated site-specific phosphotyrosine antibodies recognizing four putative regulatory residues within PLC2. Whereas all four sites were rapidly modified in response to BCR engagement in normal B cells, Btk-deficient B cells exhibited a marked reduction in phosphorylation of the Src homology 2 (SH2)-SH3 linker region sites, Tyr⁷⁵³ and Tyr⁷⁵⁹. Phosphorylation of both sites was restored by expression of Tec, but not Syk, family kinases. In contrast, phosphorylation of the PLC2 carboxyl-terminal sites, Tyr¹¹⁹⁷ and Tyr¹²¹⁷, was unaffected by the absence of functional Btk. Together, these data support a model whereby Btk/Tec kinases control sustained calcium signaling via site-specific phosphorylation of key residues within the PLC2 SH2-SH3 linker.

Received for publication, October 31, 2003 , and in revised form, April 29, 2004.

^* This work was supported, in part, by National Institutes of Health Grants HD37091 and CA81140. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶¶ Recipient of a McDonnell Scholar Award, a Leukemia and Lymphoma Society Scholar Award, and the Joan J. Drake Grant for Excellence in Cancer Research. To whom correspondence should be addressed. Tel.: 206-987-7324; Fax: 206-987-7310; E-mail: drawling{at}u.washington.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. F. Andrews and D. J. Rawlings Transitional B Cells Exhibit a B Cell Receptor-Specific Nuclear Defect in Gene Transcription J. Immunol., March 1, 2009; 182(5): 2868 - 2878. [Abstract] [Full Text] [PDF]

				M. Weber, B. Treanor, D. Depoil, H. Shinohara, N. E. Harwood, M. Hikida, T. Kurosaki, and F. D. Batista Phospholipase C-{gamma}2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen J. Exp. Med., April 14, 2008; 205(4): 853 - 868. [Abstract] [Full Text] [PDF]

				N. P. Shinners, G. Carlesso, I. Castro, K. L. Hoek, R. A. Corn, R. L. Woodland, M. L. Scott, D. Wang, and W. N. Khan Bruton's Tyrosine Kinase Mediates NF-{kappa}B Activation and B Cell Survival by B Cell-Activating Factor Receptor of the TNF-R Family J. Immunol., September 15, 2007; 179(6): 3872 - 3880. [Abstract] [Full Text] [PDF]

				Y. Bogin, C. Ainey, D. Beach, and D. Yablonski SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK PNAS, April 17, 2007; 104(16): 6638 - 6643. [Abstract] [Full Text] [PDF]

				S. Xu, K.-G. Lee, J. Huo, T. Kurosaki, and K.-P. Lam Combined deficiencies in Bruton tyrosine kinase and phospholipase C{gamma}2 arrest B-cell development at a pre-BCR+ stage Blood, April 15, 2007; 109(8): 3377 - 3384. [Abstract] [Full Text] [PDF]

				D. Khurana, L. N. Arneson, R. A. Schoon, C. J. Dick, and P. J. Leibson Differential Regulation of Human NK Cell-Mediated Cytotoxicity by the Tyrosine Kinase Itk J. Immunol., March 15, 2007; 178(6): 3575 - 3582. [Abstract] [Full Text] [PDF]

				K. M. Dennehy, F. Elias, S.-Y. Na, K.-D. Fischer, T. Hunig, and F. Luhder Mitogenic CD28 Signals Require the Exchange Factor Vav1 to Enhance TCR Signaling at the SLP-76-Vav-Itk Signalosome J. Immunol., February 1, 2007; 178(3): 1363 - 1371. [Abstract] [Full Text] [PDF]

				R. M. Hinman, J. N. Bushanam, W. A. Nichols, and A. B. Satterthwaite B Cell Receptor Signaling Down-Regulates Forkhead Box Transcription Factor Class O 1 mRNA Expression via Phosphatidylinositol 3-Kinase and Bruton's Tyrosine Kinase J. Immunol., January 15, 2007; 178(2): 740 - 747. [Abstract] [Full Text] [PDF]

				K. L. Hoek, P. Antony, J. Lowe, N. Shinners, B. Sarmah, S. R. Wente, D. Wang, R. M. Gerstein, and W. N. Khan Transitional B Cell Fate Is Associated with Developmental Stage-Specific Regulation of Diacylglycerol and Calcium Signaling upon B Cell Receptor Engagement J. Immunol., October 15, 2006; 177(8): 5405 - 5413. [Abstract] [Full Text] [PDF]

				J. Liu, M. E. Fitzgerald, M. C. Berndt, C. W. Jackson, and T. K. Gartner Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo Blood, October 15, 2006; 108(8): 2596 - 2603. [Abstract] [Full Text] [PDF]

				J. Rajaiya, J. C. Nixon, N. Ayers, Z. P. Desgranges, A. L. Roy, and C. F. Webb Induction of Immunoglobulin Heavy-Chain Transcription through the Transcription Factor Bright Requires TFII-I Mol. Cell. Biol., June 15, 2006; 26(12): 4758 - 4768. [Abstract] [Full Text] [PDF]

				S. Xu, J. Huo, W.-K. Chew, M. Hikida, T. Kurosaki, and K.-P. Lam Phospholipase C{gamma}2 Dosage Is Critical for B Cell Development in the Absence of Adaptor Protein BLNK. J. Immunol., April 15, 2006; 176(8): 4690 - 4698. [Abstract] [Full Text] [PDF]

				N. J. Horwood, T. H. Page, J. P. McDaid, C. D. Palmer, J. Campbell, T. Mahon, F. M. Brennan, D. Webster, and B. M. J. Foxwell Bruton's Tyrosine Kinase Is Required for TLR2 and TLR4-Induced TNF, but Not IL-6, Production J. Immunol., March 15, 2006; 176(6): 3635 - 3641. [Abstract] [Full Text] [PDF]

				S. Iwaki, C. Tkaczyk, A. B. Satterthwaite, K. Halcomb, M. A. Beaven, D. D. Metcalfe, and A. M. Gilfillan Btk Plays a Crucial Role in the Amplification of Fc{epsilon}RI-mediated Mast Cell Activation by Kit J. Biol. Chem., December 2, 2005; 280(48): 40261 - 40270. [Abstract] [Full Text] [PDF]

				T. Piechulek, T. Rehlen, C. Walliser, P. Vatter, B. Moepps, and P. Gierschik Isozyme-specific Stimulation of Phospholipase C-{gamma}2 by Rac GTPases J. Biol. Chem., November 25, 2005; 280(47): 38923 - 38931. [Abstract] [Full Text] [PDF]

				C. J. Serrano, L. Graham, K. DeBell, R. Rawat, M. C. Veri, E. Bonvini, B. L. Rellahan, and I. G. Reischl A New Tyrosine Phosphorylation Site in PLC{gamma}1: The Role of Tyrosine 775 in Immune Receptor Signaling J. Immunol., May 15, 2005; 174(10): 6233 - 6237. [Abstract] [Full Text] [PDF]

				J. Rajaiya, M. Hatfield, J. C. Nixon, D. J. Rawlings, and C. F. Webb Bruton's Tyrosine Kinase Regulates Immunoglobulin Promoter Activation in Association with the Transcription Factor Bright Mol. Cell. Biol., March 15, 2005; 25(6): 2073 - 2084. [Abstract] [Full Text] [PDF]

				M. E. Moreno-Garcia, L. N. Lopez-Bojorques, A. Zentella, L. A. Humphries, D. J. Rawlings, and L. Santos-Argumedo CD38 Signaling Regulates B Lymphocyte Activation via a Phospholipase C (PLC)-{gamma}2-Independent, Protein Kinase C, Phosphatidylcholine-PLC, and Phospholipase D-Dependent Signaling Cascade J. Immunol., March 1, 2005; 174(5): 2687 - 2695. [Abstract] [Full Text] [PDF]

				S. Middendorp, A. J. E. Zijlstra, R. Kersseboom, G. M. Dingjan, H. Jumaa, and R. W. Hendriks Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity Blood, January 1, 2005; 105(1): 259 - 265. [Abstract] [Full Text] [PDF]