title: Transformation suppression by protein tyrosine phosphatase 1B requires a functional SH3 ligand.
abstract: We have recently shown that protein tyrosine phosphatase 1B (PTP1B) associates with the docking protein p130Cas in 3Y1 rat fibroblasts. This interaction is mediated by a proline-rich sequence on PTP1B and the SH3 domain on p130Cas. Expression of wild-type PTP1B (WT-PTP1B), but not a catalytically competent, proline-to-alanine point mutant that cannot bind p130Cas (PA-PTP1B), causes substantial tyrosine dephosphorylation of p130Cas (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 p130Cas and two proteins that are associated with p130Cas, Paxillin and Fak. Expression of WT-PTP1B reduces formation of p130Cas-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 p130Cas may represent an important physiological target of PTP1B in cells.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: M A
authors.initials: MA
authors.lastname: Sells
authors.forename: J
authors.initials: J
authors.lastname: Chernoff
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050719:Crk-Associated Substrate Protein; D005347:Fibroblasts; D008024:Ligands; D010750:Phosphoproteins / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011506:Proteins; D011519:Proto-Oncogenes / Q000235:genetics*; D051381:Rats; D050717:Retinoblastoma-Like Protein p130; D018909:src Homology Domains / Q000235:genetics*
chemical_list: C493843:Bcar1 protein, rat; D050719:Crk-Associated Substrate Protein; D008024:Ligands; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; D017027:Protein Tyrosine Phosphatases