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Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130 Cas
Author(s) -
Weng LiangPing,
Wang Xin,
Yu Qiang
Publication year - 1999
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 - 10.1046/j.1365-2443.1999.00251.x
Subject(s) - focal adhesion , protein tyrosine phosphatase , biology , microbiology and biotechnology , tyrosine phosphorylation , cell adhesion , signal transduction , ptk2 , phosphatase , tyrosine , apoptosis , transmembrane protein , phosphorylation , cell , receptor , biochemistry , protein kinase c , mitogen activated protein kinase kinase
Background : LAR is a transmembrane receptor‐like protein tyrosine phosphatase (PTP). Genetic studies of Drosophila LAR suggest that LAR may function to regulate cell adhesions or adhesion‐mediated signal transduction. The over‐expression of LAR in mammalian tissue culture cells does not affect cell adhesion but induces caspase‐dependent apoptosis. This study investigates molecular mechanisms of LAR‐induced apoptosis by searching for in vivo substrates of LAR which are responsible for LAR‐induced apoptosis.Results : The over‐expression of LAR in tissue culture cells specifically decreased the steady state protein level of p130 Cas , a multifunctional signal assembly protein in signal transduction, by reducing the tyrosine phosphorylation and protein stability of p130 Cas . The reduction of p130 Cas protein level could be inhibited by tyrosine phosphatase inhibitors. Phosphatase domain‐deleted mutant LARs had no effect on p130 Cas . LAR also preferentially dephosphorylated p130 Cas in vitro . Subcellularly, LAR and p130 Cas were co‐localized along stress fibres and at focal adhesions. LAR over‐expression eliminated p130 Cas from focal adhesions without affecting focal adhesion assembly. Restoring the level of p130 Cas alleviated LAR‐induced apoptosis.Conclusions : p130 Cas is an in vivo substrate of LAR. LAR specifically dephosphorylates and destabilizes p130 Cas and may play a role in regulating cell adhesion‐mediated cell survival. The function of p130 Cas in focal adhesions may not be to regulate focal adhesion assembly and cell adhesion but rather to transduce the cell adhesion‐generated signals which are essential for cell survival.