Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas.
Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas.
复制标题
跨膜酪氨酸磷酸酶 LAR 通过使 p130Cas 去磷酸化和不稳定来诱导细胞凋亡。
DOI：
10.1046/j.1365-2443.1999.00251.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Yu,Q
中科院分区：
文献类型：
--
作者：
Weng,LP;Wang,X;Yu,Q
BackgroundLAR is a transmembrane receptor‐like protein tyrosine phosphatase (PTP). Genetic studies ofDrosophilaLAR 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 forin vivosubstrates of LAR which are responsible for LAR‐induced apoptosis.ResultsThe over‐expression of LAR in tissue culture cells specifically decreased the steady state protein level of p130Cas, a multifunctional signal assembly protein in signal transduction, by reducing the tyrosine phosphorylation and protein stability of p130Cas. The reduction of p130Casprotein level could be inhibited by tyrosine phosphatase inhibitors. Phosphatase domain‐deleted mutant LARs had no effect on p130Cas. LAR also preferentially dephosphorylated p130Casin vitro. Subcellularly, LAR and p130Caswere co‐localized along stress fibres and at focal adhesions. LAR over‐expression eliminated p130Casfrom focal adhesions without affecting focal adhesion assembly. Restoring the level of p130Casalleviated LAR‐induced apoptosis.Conclusionsp130Casis anin vivosubstrate of LAR. LAR specifically dephosphorylates and destabilizes p130Casand may play a role in regulating cell adhesion‐mediated cell survival. The function of p130Casin 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.
