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(Received for publication, November 18, 1996, and in revised form, May 20, 1997)
From the Molecular Oncology Group, The Tpr-Met oncoprotein consists of the catalytic
kinase domain of the hepatocyte growth factor/scatter factor receptor
tyrosine kinase (Met) fused downstream from sequences encoded by the
tpr gene. Tpr-Met is a member of a family of tyrosine
kinase oncoproteins generated following genomic rearrangement and has
constitutive kinase activity. We have previously demonstrated that a
single carboxyl-terminal tyrosine residue, Tyr489, is
essential for efficient transformation of Fr3T3 fibroblasts by Tpr-Met
and forms a multisubstrate binding site for Grb2, phosphatidylinositol 3
Volume 272, Number 32,
Issue of August 8, 1997
pp. 20167-20172
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
kinase, phospholipase C
, SHP2, and an unknown protein of 110 kDa.
A mutant Tpr-Met protein that selectively fails to bind Grb2 has
reduced transforming activity, implicating pathways downstream of Grb2
in Tpr-Met mediated cell transformation. We show here that the 110-kDa
Tpr-Met substrate corresponds to the recently identified
Grb2-associated protein, Gab1. Moreover, we show that tyrosine
phosphorylation of the Cbl protooncogene product as well as Gab1
required Tyr489 and correlated with the ability of Tpr-Met
to associate with Grb2 and to transform cells, providing evidence that
pathways downstream of Gab1 and/or Cbl may play a role in
Tpr-Met-mediated cell transformation.
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L. S. Lock, I. Royal, M. A. Naujokas, and M. Park Identification of an Atypical Grb2 Carboxyl-terminal SH3 Domain Binding Site in Gab Docking Proteins Reveals Grb2-dependent and -independent Recruitment of Gab1 to Receptor Tyrosine Kinases J. Biol. Chem., September 29, 2000; 275(40): 31536 - 31545. [Abstract] [Full Text] [PDF]
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M. Kato, K. Miyazawa, and N. Kitamura A Deubiquitinating Enzyme UBPY Interacts with the Src Homology 3 Domain of Hrs-binding Protein via a Novel Binding Motif PX(V/I)(D/N)RXXKP J. Biol. Chem., November 22, 2000; 275(48): 37481 - 37487. [Abstract] [Full Text] [PDF]
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S. Ali and S. Ali Recruitment of the Protein-tyrosine Phosphatase SHP-2 to the C-terminal Tyrosine of the Prolactin Receptor and to the Adaptor Protein Gab2 J. Biol. Chem., December 8, 2000; 275(50): 39073 - 39080. [Abstract] [Full Text] [PDF]
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W. Hung and B. Elliott Co-operative Effect of c-Src Tyrosine Kinase and Stat3 in Activation of Hepatocyte Growth Factor Expression in Mammary Carcinoma Cells J. Biol. Chem., April 6, 2001; 276(15): 12395 - 12403. [Abstract] [Full Text] [PDF]
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