Section of Molecular Carcinogenesis, Division of Hematology/Oncology, The Saban Research Institute of Childrens Hospital Los Angeles, CA 90027, USA.
BMC Biochem. 2010 Dec 1;11:48. doi: 10.1186/1471-2091-11-48.
RhoGDI proteins are important regulators of the small GTPase Rac, because they shuttle Rac from the cytoplasm to membranes and also protect Rac from activation, deactivation and degradation. How the binding and release of Rac from RhoGDI is regulated is not precisely understood.
We report that the non-receptor tyrosine kinase Fer is able to phosphorylate RhoGDIα and form a direct protein complex with it. This interaction is mediated by the C-terminal end of RhoGDIα. Activation of Fer by reactive oxygen species caused increased phosphorylation of RhoGDIα and pervanadate treatment further augmented this. Tyrosine phosphorylation of RhoGDIα by Fer prevented subsequent binding of Rac to RhoGDIα, but once a RhoGDIα-Rac complex was formed, the Fer kinase was not able to cause Rac release through tyrosine phosphorylation of preformed RhoGDIα-Rac complexes.
These results identify tyrosine phosphorylation of RhoGDIα by Fer as a mechanism to regulate binding of RhoGDIα to Rac.
RhoGDI 蛋白是小 GTP 酶 Rac 的重要调节因子，因为它们将 Rac 从细胞质穿梭到膜上，并保护 Rac 免于激活、失活和降解。RhoGDI 与 Rac 的结合和释放是如何调节的还不是很清楚。
我们报告说，非受体酪氨酸激酶 Fer 能够磷酸化 RhoGDIα 并与之形成直接的蛋白质复合物。这种相互作用是由 RhoGDIα 的 C 末端介导的。活性氧引起 Fer 的激活导致 RhoGDIα 的磷酸化增加，而过氧化物酶处理进一步增强了这种磷酸化。Fer 对 RhoGDIα 的酪氨酸磷酸化阻止了 Rac 随后与 RhoGDIα 的结合，但一旦形成了 RhoGDIα-Rac 复合物，Fer 激酶就不能通过磷酸化预先形成的 RhoGDIα-Rac 复合物来引起 Rac 释放。
这些结果表明，Fer 对 RhoGDIα 的酪氨酸磷酸化是调节 RhoGDIα 与 Rac 结合的一种机制。
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