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Extracellular domain dependence of PTPα transforming activity
Author(s) -
TremperWells Barbara,
Resnick Ross J.,
Zheng Xinmin,
Holsinger Leslie J.,
Shalloway David
Publication year - 2010
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01410.x
Subject(s) - gene isoform , biology , extracellular , phosphorylation , transmembrane protein , proto oncogene tyrosine protein kinase src , protein tyrosine phosphatase , microbiology and biotechnology , dephosphorylation , tyrosine , tyrosine phosphorylation , transmembrane domain , transformation (genetics) , phosphatase , biochemistry , amino acid , receptor , gene
Two isoforms of the transmembrane protein tyrosine phosphatase PTPα, which differ by nine amino acids in their extracellular regions, are expressed in a tissue‐specific manner. Over‐expression of the shorter isoform transforms rodent cells, and it has previously been reasonable to assume that this was a direct consequence of its dephosphorylation and activation of Src. Transformation by the longer wild‐type isoform has not previously been studied. We tested the activities of both isoforms in NIH3T3 cells and found that, while both dephosphorylated and activated Src similarly, only the shorter isoform induced focus formation or anchorage‐independent growth. Differences in phosphorylation of PTPα at its known regulatory sites, Grb2 binding to PTPα, phosphorylation level of focal adhesion kinase by PTPα, or overall localization were excluded as possible explanations for the differences in transforming activities. The results suggest that transformation by PTPα involves at least one function other than, or in addition to, its activation of Src and that this depends on PTPα’s extracellular domain. Previous studies have suggested that PTPα might be a useful target in breast and colon cancer therapy, and the results presented here suggest that it may be advantageous to develop isoform‐specific therapeutic reagents.