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Liu F , Sells MA , Chernoff J
Transformation suppression by protein tyrosine phosphatase 1B requires a functional SH3 ligand
Molecular and Cellular Biology. 1998 Jan;18(1) :250-259
PMID: ISI:000071195700026   
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Abstract
We have recently shown that protein tyrosine phosphatase 1B (PTP1B) associates with the docking protein p130(Cas) in 3Y1 rat fibroblasts, This interaction is mediated by a proline-rich sequence on PTP1B and the SN3 domain on p130(Cas), Expression of wild-type PTP1B (WT-PTP1B), but not a catalytically competent, proline-to-alanine point mutant that cannot bind p130(Cas) (PA-PTP1B), causes substantial tyrosine dephosphorylation of p130(Cas) (F, Liu, D, E, Hill, and J, Chernoff J. Biol. Chem, 271:31290-31295, 1996), Here we demonstrate that WT-, but not PA-PTP1B, inhibits transformation of rat 3Y1 fibroblasts by v-crk, -src, and -ras, but not by v- raf. These effects on transformation correlate with the phosphorylation status of p130(Cas) and two proteins that are associated with p130(Cas), Paxillin and Fak, Expression of WT- PTP1B reduces formation of p130(Cas)-Crk complexes and inhibits mitogen-activated protein kinase activation by Src and Crk. These data show that transformation suppression by PTP1B requires a functional SH3 ligand and suggest that p130(Cas) may represent an important physiological target of PTP1B in cells.
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Times Cited: 27 English Article YN687 MOL CELL BIOL