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

This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, J. Articles by Sap, J. Search for Related Content PubMed PubMed Citation Articles by Su, J. Articles by Sap, J. Social Bookmarking                      What's this?

Volume 271, Number 45, Issue of November 8, 1996 pp. 28086-28096
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Association between Receptor Protein-tyrosine Phosphatase RPTP and the Grb2 Adaptor
DUAL Src HOMOLOGY (SH) 2/SH3 DOMAIN REQUIREMENT AND FUNCTIONAL CONSEQUENCES

(Received for publication, May 20, 1996, and in revised form, July 30, 1996)

From the Department of Pharmacology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016

Receptor protein-tyrosine phosphatase RPTP is found associated in vivo with the adaptor protein Grb2. Formation of this complex, which contains no detectable levels of Sos, is known to depend on a C-terminal phosphorylated tyrosine residue (Tyr⁷⁹⁸) in RPTP and on the Src homology (SH) 2 domain in Grb2 (, ). We show here that association of Grb2 with RPTP also involves a critical function for the C-terminal SH3 domain of Grb2. Furthermore, Grb2 SH3 binding peptides interfere with RPTP-Grb2 association in vitro, and the RPTP protein can dissociate the Grb2-Sos complex in vivo. These observations constitute a novel mode of Grb2 association and suggest a model in which association with a tyrosine-phosphorylated protein restricts the repertoire of SH3 binding proteins with which Grb2 can simultaneously interact. The function of the Tyr⁷⁹⁸ tyrosine phosphorylation/Grb2 binding site in RPTP was studied further by expression of wild type or mutant RPTP proteins in PC12 cells. In these cells, wild type RPTP interferes with acidic fibroblast growth factor-induced neurite outgrowth; this effect requires both the catalytic activity and the Grb2 binding Tyr⁷⁹⁸ residue in RPTP. In contrast, expression of catalytically active RPTP containing a mutated tyrosine phosphorylation/Grb2 association site enhances neurite outgrowth. Our observations associate a functional effect with tyrosine phosphorylation of, and ensuing association of signaling proteins with, a receptor protein-tyrosine phosphatase and raise the possibility that RPTP association may modulate Grb2 function and vice versa.

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

This article has been cited by other articles:

				Q. Hao, S. A. Rutherford, B. Low, and H. Tang Suppression of the Phosphorylation of Receptor Tyrosine Phosphatase-{alpha} on the Src-Independent Site Tyrosine 789 by Reactive Oxygen Species Mol. Pharmacol., June 1, 2006; 69(6): 1938 - 1944. [Abstract] [Full Text] [PDF]

				A. Kostic and M. P. Sheetz Fibronectin Rigidity Response through Fyn and p130Cas Recruitment to the Leading Edge Mol. Biol. Cell, June 1, 2006; 17(6): 2684 - 2695. [Abstract] [Full Text] [PDF]

				A. I. Vulin, K. K. Jacob, and F. M. Stanley Integrin Activates Receptor-Like Protein Tyrosine Phosphatase {alpha}, Src, and Rho to Increase Prolactin Gene Expression through a Final Phosphatidylinositol 3-Kinase/Cytoskeletal Pathway that Is Additive with Insulin Endocrinology, August 1, 2005; 146(8): 3535 - 3546. [Abstract] [Full Text] [PDF]

				A. W Stoker Protein tyrosine phosphatases and signalling J. Endocrinol., April 1, 2005; 185(1): 19 - 33. [Abstract] [Full Text] [PDF]

				S. P. Zamora-Leon, A. Bresnick, J. M. Backer, and B. Shafit-Zagardo Fyn Phosphorylates Human MAP-2c on Tyrosine 67 J. Biol. Chem., January 21, 2005; 280(3): 1962 - 1970. [Abstract] [Full Text] [PDF]

				V. Bodrikov, I. Leshchyns'ka, V. Sytnyk, J. Overvoorde, J. den Hertog, and M. Schachner RPTP{alpha} is essential for NCAM-mediated p59fyn activation and neurite elongation J. Cell Biol., January 3, 2005; 168(1): 127 - 139. [Abstract] [Full Text] [PDF]

				H. Lu, P. Shah, D. Ennis, G. Shinder, J. Sap, H. Le-Tien, and I. G. Fantus The Differentiation of Skeletal Muscle Cells Involves a Protein-tyrosine Phosphatase-alpha -mediated C-Src Signaling Pathway J. Biol. Chem., November 22, 2002; 277(48): 46687 - 46695. [Abstract] [Full Text] [PDF]

				T.-H. Nguyen, J. Liu, and P. J. Lombroso Striatal Enriched Phosphatase 61 Dephosphorylates Fyn at Phosphotyrosine 420 J. Biol. Chem., June 28, 2002; 277(27): 24274 - 24279. [Abstract] [Full Text] [PDF]

				X.-M. Zheng, R. J. Resnick, and D. Shalloway Mitotic Activation of Protein-tyrosine Phosphatase alpha and Regulation of Its Src-mediated Transforming Activity by Its Sites of Protein Kinase C Phosphorylation J. Biol. Chem., June 7, 2002; 277(24): 21922 - 21929. [Abstract] [Full Text] [PDF]

				G. Jiang, J. den Hertog, and T. Hunter Receptor-Like Protein Tyrosine Phosphatase alpha Homodimerizes on the Cell Surface Mol. Cell. Biol., August 15, 2000; 20(16): 5917 - 5929. [Abstract] [Full Text]

				C. Blanchetot and J. den Hertog Multiple Interactions between Receptor Protein-tyrosine Phosphatase (RPTP) alpha and Membrane-distal Protein-tyrosine Phosphatase Domains of Various RPTPs J. Biol. Chem., April 21, 2000; 275(17): 12446 - 12452. [Abstract] [Full Text] [PDF]

				B. J. Goldstein, A. Bittner-Kowalczyk, M. F. White, and M. Harbeck Tyrosine Dephosphorylation and Deactivation of Insulin Receptor Substrate-1 by Protein-tyrosine Phosphatase 1B. POSSIBLE FACILITATION BY THE FORMATION OF A TERNARY COMPLEX WITH THE GRB2 ADAPTOR PROTEIN J. Biol. Chem., February 11, 2000; 275(6): 4283 - 4289. [Abstract] [Full Text] [PDF]

				R. Lammers, M. M. Lerch, and A. Ullrich The Carboxyl-terminal Tyrosine Residue of Protein-tyrosine Phosphatase alpha Mediates Association with Focal Adhesion Plaques J. Biol. Chem., February 4, 2000; 275(5): 3391 - 3396. [Abstract] [Full Text] [PDF]

				V. Bhandari, K. L. Lim, and C. J. Pallen Physical and Functional Interactions between Receptor-like Protein-tyrosine Phosphatase alpha  and p59fyn J. Biol. Chem., April 10, 1998; 273(15): 8691 - 8698. [Abstract] [Full Text] [PDF]

				K. K. Jacob, J. Sap, and F. M. Stanley Receptor-like Protein-tyrosine Phosphatase alpha  Specifically Inhibits Insulin-increased Prolactin Gene Expression J. Biol. Chem., February 20, 1998; 273(8): 4800 - 4809. [Abstract] [Full Text] [PDF]

				L. Liang, K. L. Lim, K. T. Seow, C. H. Ng, and C. J. Pallen Calmodulin Binds to and Inhibits the Activity of the Membrane Distal Catalytic Domain of Receptor Protein-tyrosine Phosphatase alpha J. Biol. Chem., September 22, 2000; 275(39): 30075 - 30081. [Abstract] [Full Text] [PDF]