This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pasquet, J.-M.
Right arrow Articles by Watson, S. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pasquet, J.-M.
Right arrow Articles by Watson, S. P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 1999, p. 8326-8334, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

LAT Is Required for Tyrosine Phosphorylation of Phospholipase Cgamma 2 and Platelet Activation by the Collagen Receptor GPVI

Jean-Max Pasquet,1,* Barbara Gross,1 Lynn Quek,1 Naoki Asazuma,1 Weiguo Zhang,2 Connie L. Sommers,3 Edina Schweighoffer,4 Victor Tybulewicz,4 Barbara Judd,5 Jong Ran Lee,5 Gary Koretzky,5 Paul E. Love,3 Lawrence E. Samelson,2 and Steve P. Watson1

Department of Pharmacology, University of Oxford, Oxford OX1 3QT,1 and Division of Cellular Immunology, National Institute for Medical Research, Mill Hill, London NW7 1AA,4 United Kingdom; Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 522425; and Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development,3 and Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch,2 National Institutes of Health, Bethesda, Maryland 20892

Received 27 May 1999/Returned for modification 20 July 1999/Accepted 27 July 1999

In the present study, we have addressed the role of the linker for activation of T cells (LAT) in the regulation of phospholipase Cgamma 2 (PLCgamma 2) by the platelet collagen receptor glycoprotein VI (GPVI). LAT is tyrosine phosphorylated in human platelets heavily in response to collagen, collagen-related peptide (CRP), and Fcgamma RIIA cross-linking but only weakly in response to the G-protein-receptor-coupled agonist thrombin. LAT tyrosine phosphorylation is abolished in CRP-stimulated Syk-deficient mouse platelets, whereas it is not altered in SLP-76-deficient mice or Btk-deficient X-linked agammaglobulinemia (XLA) human platelets. Using mice engineered to lack the adapter LAT, we showed that tyrosine phosphorylation of Syk and Btk in response to CRP was maintained in LAT-deficient platelets whereas phosphorylation of SLP-76 was slightly impaired. In contrast, tyrosine phosphorylation of PLCgamma 2 was substantially reduced in LAT-deficient platelets but was not completely inhibited. The reduction in phosphorylation of PLCgamma 2 was associated with marked inhibition of formation of phosphatidic acid, a metabolite of 1,2-diacylglycerol, phosphorylation of pleckstrin, a substrate of protein kinase C, and expression of P-selectin in response to CRP, whereas these parameters were not altered in response to thrombin. Activation of the fibrinogen receptor integrin alpha IIbbeta 3 in response to CRP was also reduced in LAT-deficient platelets but was not completely inhibited. These results demonstrate that LAT tyrosine phosphorylation occurs downstream of Syk and is independent of the adapter SLP-76, and they establish a major role for LAT in the phosphorylation and activation of PLCgamma 2, leading to downstream responses such as alpha -granule secretion and activation of integrin alpha IIbbeta 3. The results further demonstrate that the major pathway of tyrosine phosphorylation of SLP-76 is independent of LAT and that there is a minor, LAT-independent pathway of tyrosine phosphorylation of PLCgamma 2. We propose a model in which LAT and SLP-76 are required for PLCgamma 2 phosphorylation but are regulated through independent pathways downstream of Syk.

* Corresponding author. Mailing address: Department of Pharmacology, University of Oxford, Mansfield Rd., Oxford OX1 3QT, United Kingdom. Phone: (44) 1865 271592. Fax: (44) 1865 271 853. E-mail: max.pasquet{at}pharm.ox.ac.uk.

Molecular and Cellular Biology, December 1999, p. 8326-8334, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Senis, Y. A., Tomlinson, M. G., Ellison, S., Mazharian, A., Lim, J., Zhao, Y., Kornerup, K. N., Auger, J. M., Thomas, S. G., Dhanjal, T., Kalia, N., Zhu, J. W., Weiss, A., Watson, S. P. (2009). The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis. Blood 113: 4942-4954 [Abstract] [Full Text]  
  • Whittaker, G. C., Burshtyn, D. N., Orr, S. J., Quigley, L., Hodge, D. L., Pascal, V., Zhang, W., McVicar, D. W. (2008). Analysis of the linker for activation of T cells and the linker for activation of B cells in natural killer cells reveals a novel signaling cassette, dual usage in ITAM signaling, and influence on development of the Ly49 repertoire. Blood 112: 2869-2877 [Abstract] [Full Text]  
  • Ohmori, T., Kashiwakura, Y., Ishiwata, A., Madoiwa, S., Mimuro, J., Sakata, Y. (2007). Silencing of a Targeted Protein in In Vivo Platelets Using a Lentiviral Vector Delivering Short Hairpin RNA Sequence. Arterioscler. Thromb. Vasc. Bio. 27: 2266-2272 [Abstract] [Full Text]  
  • Ragab, A., Severin, S., Gratacap, M.-P., Aguado, E., Malissen, M., Jandrot-Perrus, M., Malissen, B., Ragab-Thomas, J., Payrastre, B. (2007). Roles of the C-terminal tyrosine residues of LAT in GPVI-induced platelet activation: insights into the mechanism of PLC{gamma}2 activation. Blood 110: 2466-2474 [Abstract] [Full Text]  
  • Rabie, T., Varga-Szabo, D., Bender, M., Pozgaj, R., Lanza, F., Saito, T., Watson, S. P., Nieswandt, B. (2007). Diverging signaling events control the pathway of GPVI down-regulation in vivo. Blood 110: 529-535 [Abstract] [Full Text]  
  • Abtahian, F., Bezman, N., Clemens, R., Sebzda, E., Cheng, L., Shattil, S. J., Kahn, M. L., Koretzky, G. A. (2006). Evidence for the Requirement of ITAM Domains but Not SLP-76/Gads Interaction for Integrin Signaling in Hematopoietic Cells.. Mol. Cell. Biol. 26: 6936-6949 [Abstract] [Full Text]  
  • Suzuki-Inoue, K., Fuller, G. L. J., Garcia, A., Eble, J. A., Pohlmann, S., Inoue, O., Gartner, T. K., Hughan, S. C., Pearce, A. C., Laing, G. D., Theakston, R. D. G., Schweighoffer, E., Zitzmann, N., Morita, T., Tybulewicz, V. L. J., Ozaki, Y., Watson, S. P. (2006). A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 107: 542-549 [Abstract] [Full Text]  
  • Liu, J., Pestina, T. I., Berndt, M. C., Jackson, C. W., Gartner, T. K. (2005). Botrocetin/VWF-induced signaling through GPIb-IX-V produces TxA2 in an {alpha}IIb{beta}3- and aggregation-independent manner. Blood 106: 2750-2756 [Abstract] [Full Text]  
  • Sarratt, K. L., Chen, H., Zutter, M. M., Santoro, S. A., Hammer, D. A., Kahn, M. L. (2005). GPVI and {alpha}2{beta}1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood 106: 1268-1277 [Abstract] [Full Text]  
  • Dangelmaier, C. A., Quinter, P. G., Jin, J., Tsygankov, A. Y., Kunapuli, S. P., Daniel, J. L. (2005). Rapid ubiquitination of Syk following GPVI activation in platelets. Blood 105: 3918-3924 [Abstract] [Full Text]  
  • Pearce, A. C., Senis, Y. A., Billadeau, D. D., Turner, M., Watson, S. P., Vigorito, E. (2004). Vav1 and Vav3 Have Critical but Redundant Roles in Mediating Platelet Activation by Collagen. J. Biol. Chem. 279: 53955-53962 [Abstract] [Full Text]  
  • Gibbins, J. M. (2004). Platelet adhesion signalling and the regulation of thrombus formation. J. Cell Sci. 117: 3415-3425 [Abstract] [Full Text]  
  • Atkinson, B. T., Ellmeier, W., Watson, S. P. (2003). Tec regulates platelet activation by GPVI in the absence of Btk. Blood 102: 3592-3599 [Abstract] [Full Text]  
  • Ragab, A., Bodin, S., Viala, C., Chap, H., Payrastre, B., Ragab-Thomas, J. (2003). The Tyrosine Phosphatase 1B Regulates Linker for Activation of T-cell Phosphorylation and Platelet Aggregation upon Fc{gamma}RIIa Cross-linking. J. Biol. Chem. 278: 40923-40932 [Abstract] [Full Text]  
  • Wonerow, P., Pearce, A. C., Vaux, D. J., Watson, S. P. (2003). A Critical Role for Phospholipase C{gamma}2 in {alpha}IIb{beta}3-mediated Platelet Spreading. J. Biol. Chem. 278: 37520-37529 [Abstract] [Full Text]  
  • Goncalves, I., Hughan, S. C., Schoenwaelder, S. M., Yap, C. L., Yuan, Y., Jackson, S. P. (2003). Integrin {alpha}IIb{beta}3-dependent Calcium Signals Regulate Platelet-Fibrinogen Interactions under Flow: INVOLVEMENT OF PHOSPHOLIPASE C{gamma}2. J. Biol. Chem. 278: 34812-34822 [Abstract] [Full Text]  
  • Suzuki-Inoue, K., Inoue, O., Frampton, J., Watson, S. P. (2003). Murine GPVI stimulates weak integrin activation in PLC{gamma}2-/- platelets: involvement of PLC{gamma}1 and PI3-kinase. Blood 102: 1367-1373 [Abstract] [Full Text]  
  • Chen, H., Kahn, M. L. (2003). Reciprocal Signaling by Integrin and Nonintegrin Receptors during Collagen Activation of Platelets. Mol. Cell. Biol. 23: 4764-4777 [Abstract] [Full Text]  
  • Nieswandt, B., Watson, S. P. (2003). Platelet-collagen interaction: is GPVI the central receptor?. Blood 102: 449-461 [Abstract] [Full Text]  
  • Watanabe, N., Nakajima, H., Suzuki, H., Oda, A., Matsubara, Y., Moroi, M., Terauchi, Y., Kadowaki, T., Suzuki, H., Koyasu, S., Ikeda, Y., Handa, M. (2003). Functional phenotype of phosphoinositide 3-kinase p85{alpha}-null platelets characterized by an impaired response to GP VI stimulation. Blood 102: 541-548 [Abstract] [Full Text]  
  • Locke, D., Liu, C., Peng, X., Chen, H., Kahn, M. L. (2003). Fc Rgamma -independent Signaling by the Platelet Collagen Receptor Glycoprotein VI. J. Biol. Chem. 278: 15441-15448 [Abstract] [Full Text]  
  • Cho, M. J., Liu, J., Pestina, T. I., Steward, S. A., Thomas, D. W., Coffman, T. M., Wang, D., Jackson, C. W., Gartner, T. K. (2003). The roles of alpha IIbbeta 3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation. Blood 101: 2646-2651 [Abstract] [Full Text]  
  • Pearce, A. C., Wilde, J. I., Doody, G. M., Best, D., Inoue, O., Vigorito, E., Tybulewicz, V. L. J., Turner, M., Watson, S. P. (2002). Vav1, but not Vav2, contributes to platelet aggregation by CRP and thrombin, but neither is required for regulation of phospholipase C. Blood 100: 3561-3569 [Abstract] [Full Text]  
  • Du, X.-Y., Clemetson, J. M., Navdaev, A., Magnenat, E. M., Wells, T. N. C., Clemetson, K. J. (2002). Ophioluxin, a Convulxin-like C-type Lectin from Ophiophagus hannah (King Cobra) Is a Powerful Platelet Activator via Glycoprotein VI. J. Biol. Chem. 277: 35124-35132 [Abstract] [Full Text]  
  • Suzuki-Inoue, K., Tulasne, D., Shen, Y., Bori-Sanz, T., Inoue, O., Jung, S. M., Moroi, M., Andrews, R. K., Berndt, M. C., Watson, S. P. (2002). Association of Fyn and Lyn with the Proline-rich Domain of Glycoprotein VI Regulates Intracellular Signaling. J. Biol. Chem. 277: 21561-21566 [Abstract] [Full Text]  
  • Judd, B. A., Myung, P. S., Obergfell, A., Myers, E. E., Cheng, A. M., Watson, S. P., Pear, W. S., Allman, D., Shattil, S. J., Koretzky, G. A. (2002). Differential Requirement for LAT and SLP-76 in GPVI versus T Cell Receptor Signaling. JEM 195: 705-717 [Abstract] [Full Text]  
  • Suzuki-Inoue, K., Yatomi, Y., Asazuma, N., Kainoh, M., Tanaka, T., Satoh, K., Ozaki, Y. (2001). Rac, a small guanosine triphosphate-binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surfaces: roles of integrin alpha 2beta 1. Blood 98: 3708-3716 [Abstract] [Full Text]  
  • Wilson, B. S., Pfeiffer, J. R., Surviladze, Z., Gaudet, E. A., Oliver, J. M. (2001). High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc{epsilon}RI and LAT. JCB 154: 645-658 [Abstract] [Full Text]  
  • Sommers, C. L., Menon, R. K., Grinberg, A., Zhang, W., Samelson, L. E., Love, P. E. (2001). Knock-in Mutation of the Distal Four Tyrosines of Linker for Activation of T Cells Blocks Murine T Cell Development. JEM 194: 135-142 [Abstract] [Full Text]  
  • Wu, Y., Suzuki-Inoue, K., Satoh, K., Asazuma, N., Yatomi, Y., Berndt, M. C., Ozaki, Y. (2001). Role of Fc receptor {gamma}-chain in platelet glycoprotein Ib-mediated signaling. Blood 97: 3836-3845 [Abstract] [Full Text]  
  • Patil, S., Newman, D. K., Newman, P. J. (2001). Platelet endothelial cell adhesion molecule-1 serves as an inhibitory receptor that modulates platelet responses to collagen. Blood 97: 1727-1732 [Abstract] [Full Text]  
  • Bobe, R., Wilde, J. I., Maschberger, P., Venkateswarlu, K., Cullen, P. J., Siess, W., Watson, S. P. (2001). Phosphatidylinositol 3-kinase-dependent translocation of phospholipase C{gamma}2 in mouse megakaryocytes is independent of Bruton tyrosine kinase translocation. Blood 97: 678-684 [Abstract] [Full Text]  
  • Falet, H., Barkalow, K. L., Pivniouk, V. I., Barnes, M. J., Geha, R. S., Hartwig, J. H. (2000). Roles of SLP-76, phosphoinositide 3-kinase, and gelsolin in the platelet shape changes initiated by the collagen receptor GPVI/FcRgamma -chain complex. Blood 96: 3786-3792 [Abstract] [Full Text]  
  • Judd, B. A., Myung, P. S., Leng, L., Obergfell, A., Pear, W. S., Shattil, S. J., Koretzky, G. A. (2000). Hematopoietic reconstitution of SLP-76 corrects hemostasis and platelet signaling through alpha IIbbeta 3 and collagen receptors. Proc. Natl. Acad. Sci. USA 97: 12056-12061 [Abstract] [Full Text]  
  • Pasquet, J.-m., Gross, B. S., Gratacap, M.-P., Quek, L., Pasquet, S., Payrastre, B., van Willigen, G., Mountford, J. C., Watson, S. P. (2000). Thrombopoietin potentiates collagen receptor signaling in platelets through a phosphatidylinositol 3-kinase-dependent pathway. Blood 95: 3429-3434 [Abstract] [Full Text]  
  • Asazuma, N., Wilde, J. I., Berlanga, O., Leduc, M., Leo, A., Schweighoffer, E., Tybulewicz, V., Bon, C., Liu, S. K., McGlade, C. J., Schraven, B., Watson, S. P. (2000). Interaction of Linker for Activation of T Cells with Multiple Adapter Proteins in Platelets Activated by the Glycoprotein VI-selective Ligand, Convulxin. J. Biol. Chem. 275: 33427-33434 [Abstract] [Full Text]  
  • Pasquet, J.-M., Quek, L., Pasquet, S., Poole, A., Matthews, J. R., Lowell, C., Watson, S. P. (2000). Evidence of a Role for SHP-1 in Platelet Activation by the Collagen Receptor Glycoprotein VI. J. Biol. Chem. 275: 28526-28531 [Abstract] [Full Text]  
  • Schulte, V., Snell, D., Bergmeier, W., Zirngibl, H., Watson, S. P., Nieswandt, B. (2001). Evidence for Two Distinct Epitopes within Collagen for Activation of Murine Platelets. J. Biol. Chem. 276: 364-368 [Abstract] [Full Text]  
  • Canobbio, I., Bertoni, A., Lova, P., Paganini, S., Hirsch, E., Sinigaglia, F., Balduini, C., Torti, M. (2001). Platelet Activation by von Willebrand Factor Requires Coordinated Signaling through Thromboxane A2 and Fcgamma IIA Receptor. J. Biol. Chem. 276: 26022-26029 [Abstract] [Full Text]  
  • Geng, L., Pfister, S., Kraeft, S.-K., Rudd, C. E. (2001). Adaptor FYB (Fyn-binding protein) regulates integrin-mediated adhesion and mediator release: Differential involvement of the FYB SH3 domain. Proc. Natl. Acad. Sci. USA 98: 11527-11532 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»