Lu Ning, Guarnieri Douglas J, Simon Michael A
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
EMBO J. 2004 Mar 10;23(5):1089-100. doi: 10.1038/sj.emboj.7600127. Epub 2004 Feb 19.
Two tyrosine kinases, Src64 and Tec29, regulate the growth of actin rich-ring canals in the Drosophila ovary. We have shown previously that Src64 directs the localization of Tec29 to ring canals, but the mechanism underlying this process was unknown. Here, we show that Tec29 localizes to ring canals via its Src homology 3 (SH3) and Src homology 2 (SH2) domains. Tec29 activity is required for its own ring canal localization, suggesting that a phosphotyrosine ligand for the SH2 domain is generated by Tec29 itself. Src64 regulates this process by phosphorylating Y677 within the kinase domain of Tec29, an event required for Tec29 activation. We also show that the pleckstrin homology (PH) domain of Tec29 has dual functions in mediating Src64 regulation. In the absence of Src64, the PH domain prevents Tec29 ring canal localization. In the presence of Src64, it enhances membrane targeting of Tec29 by a PI(3,4,5)P(3)-mediated mechanism. In the absence of its PH domain, Tec29 constitutively localizes to ring canals, but still requires Src64 for full activation.
两种酪氨酸激酶，Src64和Tec29，调节果蝇卵巢中富含肌动蛋白的环管的生长。我们之前已经表明，Src64将Tec29定位到环管，但这一过程的潜在机制尚不清楚。在这里，我们表明Tec29通过其Src同源3（SH3）和Src同源2（SH2）结构域定位于环管。Tec29的活性是其自身环管定位所必需的，这表明SH2结构域的磷酸酪氨酸配体是由Tec29自身产生的。Src64通过磷酸化Tec29激酶结构域内的Y677来调节这一过程，这是Tec29激活所必需的事件。我们还表明，Tec29的普列克底物蛋白同源（PH）结构域在介导Src64调节方面具有双重功能。在没有Src64的情况下，PH结构域阻止Tec29环管定位。在有Src64的情况下，它通过PI(3,4,5)P(3)介导的机制增强Tec29的膜靶向作用。在没有其PH结构域的情况下，Tec29组成性地定位于环管，但仍需要Src64进行完全激活。
