Walker F, deBlaquiere J, Burgess A W
Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia.
J Biol Chem. 1993 Sep 15;268(26):19552-8.
The src family of protein-tyrosine kinases has long been implicated in signal transduction by growth factor receptors. In particular, pp60c-src, the product of the protooncogene c-src, has been shown to associated with the activated platelet-derived growth factor (PDGF) receptor. We demonstrate that, following stimulation of quiescent cells with PDGF, pp60c-src is translocated from the plasma membrane to the cytosol. This phenomenon was better defined utilizing an isolated plasma membrane system. The release of pp60c-src from the membrane in response to PDGF is accompanied by a 4-fold activation of its kinase activity and by phosphorylation at the amino terminus on serine/threonine residues as well as tyrosine residues. This amino-terminal phosphorylation appears to be responsible for a change in hydrophobicity of the pp60c-src molecule and hence for its release from the membrane. The kinase responsible for the serine/threonine phosphorylation and the concomitant release of pp60c-src has been identified as the cAMP-dependent protein kinase. Thus, PDGF stimulation activates at least two membrane-associated kinases (pp60c-src and cAMP-dependent protein kinase) very early in its signal transduction pathway.
蛋白质酪氨酸激酶的src家族长期以来一直被认为与生长因子受体的信号转导有关。特别是原癌基因c-src的产物pp60c-src，已被证明与活化的血小板衍生生长因子（PDGF）受体相关。我们证明，在用PDGF刺激静止细胞后，pp60c-src从质膜转移到细胞质中。利用分离的质膜系统能更好地明确这一现象。响应PDGF时，pp60c-src从膜上释放，同时其激酶活性被激活4倍，并且在丝氨酸/苏氨酸残基以及酪氨酸残基的氨基末端发生磷酸化。这种氨基末端磷酸化似乎导致了pp60c-src分子疏水性的改变，从而使其从膜上释放。负责丝氨酸/苏氨酸磷酸化以及pp60c-src随之释放的激酶已被鉴定为cAMP依赖性蛋白激酶。因此，PDGF刺激在其信号转导途径的很早阶段就激活了至少两种与膜相关的激酶（pp60c-src和cAMP依赖性蛋白激酶）。
