ROLE OF P34(CDC2)-MEDIATED PHOSPHORYLATIONS IN 2-STEP ACTIVATION OF PP60(C-SRC) DURING MITOSIS
ROLE OF P34(CDC2)-MEDIATED PHOSPHORYLATIONS IN 2-STEP ACTIVATION OF PP60(C-SRC) DURING MITOSIS
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DOI：
10.1073/pnas.89.15.7237
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发表时间：
1992-08-01
影响因子：
11.1
通讯作者：
SHALLOWAY, D
中科院分区：
文献类型：
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作者：
SHENOY, S;CHACKALAPARAMPIL, I;SHALLOWAY, D
P34cdc2在三个氨基近端的丝氨酸/苏氨酸残基上对pp60c-src的磷酸化与c-src的有丝分裂激活有时间上的相关性，但不足以促进c-src的有丝分裂激活。有丝分裂期间激活的直接原因似乎与Tyr-527的部分去磷酸化有关，Tyr-527是一种残基，其磷酸化强烈抑制pp60c-src的活性。丝氨酸/苏氨酸磷酸化位点的定点突变阻止了有丝分裂特异性Tyr-527磷酸化降低的一半和pp60c-src激酶活性增加的一半。我们得出结论，p34cdc2通过两个步骤部分激活pp60c-src，在这个过程中，其丝氨酸/苏氨酸磷酸化要么使pp60c-src对Tyr-527磷酸酶敏感，要么使其对Tyr-527激酶不敏感。此外，与p34cdc2介导的磷酸化无关的其他事件也参与了pp60c-src的有丝分裂激活。
Phosphorylation of pp60c-src by p34cdc2 at three amino-proximal serine/threonine residues is temporally correlated with, but insufficient for, mitotic activation of c-Src kinase. The direct cause of activation during mitosis appears to be temporally correlated partial dephosphorylation of Tyr-527, a residue whose phosphorylation strongly suppresses pp60c-src activity. Site-directed mutagenesis of the serine/threonine phosphorylation sites blocks half the mitosis-specific decrease in Tyr-527 phosphorylation and half the increase in pp60c-src kinase activity. We conclude that p34cdc2 partially activates pp60c-src by a two-step process in which its serine/threonine phosphorylations either sensitize pp60c-src to a Tyr-527 phosphatase or desensitize it to a Tyr-527 kinase. Furthermore, additional events, independent of these p34cdc2-mediated phosphorylations, participate in mitotic activation of pp60c-src.