Chang B Y, Chiang M, Cartwright C A
Department of Medicine, Stanford University, Stanford, California 94305, USA.
J Biol Chem. 2001 Jun 8;276(23):20346-56. doi: 10.1074/jbc.M101375200. Epub 2001 Mar 8.
RACK1 is an intracellular receptor for the serine/ threonine protein kinase C. Previously, we demonstrated that RACK1 also interacts with the Src protein-tyrosine kinase. RACK1, via its association with these protein kinases, may play a key role in signal transduction. To further characterize the Src-RACK1 interaction and to analyze mechanisms by which cross-talk occurs between the two RACK1-linked signaling kinases, we identified sites on Src and RACK1 that mediate their binding, and factors that regulate their interaction. We found that the interaction of Src and RACK1 is mediated, in part, by the SH2 domain of Src and by phosphotyrosines in the sixth WD repeat of RACK1, and is enhanced by serum or platelet-derived growth factor stimulation, protein kinase C activation, and tyrosine phosphorylation of RACK1. To the best of our knowledge, this is the first report of tyrosine phosphorylation of a member of the WD repeat family of proteins. We think that tyrosine phosphorylation of these proteins is an important mechanism of signal transduction in cells.
RACK1是丝氨酸/苏氨酸蛋白激酶C的一种细胞内受体。此前，我们证明RACK1还与Src蛋白酪氨酸激酶相互作用。RACK1通过与这些蛋白激酶的结合，可能在信号转导中起关键作用。为了进一步表征Src与RACK1的相互作用，并分析这两种与RACK1相关的信号激酶之间发生串扰的机制，我们确定了Src和RACK1上介导它们结合的位点，以及调节它们相互作用的因子。我们发现，Src与RACK1的相互作用部分由Src的SH2结构域和RACK1第六个WD重复序列中的磷酸酪氨酸介导，并通过血清或血小板衍生生长因子刺激、蛋白激酶C激活以及RACK1的酪氨酸磷酸化而增强。据我们所知，这是关于WD重复蛋白家族成员酪氨酸磷酸化的首次报道。我们认为这些蛋白的酪氨酸磷酸化是细胞中信号转导的重要机制。
