REQUIREMENT FOR INTEGRATION OF SIGNALS FROM 2 DISTINCT PHOSPHORYLATION PATHWAYS FOR ACTIVATION OF MAP KINASE
REQUIREMENT FOR INTEGRATION OF SIGNALS FROM 2 DISTINCT PHOSPHORYLATION PATHWAYS FOR ACTIVATION OF MAP KINASE
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DOI：
10.1038/343651a0
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发表时间：
1990-02-15
期刊：
影响因子：
64.8
通讯作者：
STURGILL, TW
中科院分区：
文献类型：
--
作者：
ANDERSON, NG;MALLER, JL;STURGILL, TW
MAP激酶（相对分子质量，42，000）是一种低丰度丝氨酸-苏氨酸蛋白激酶，在许多细胞类型中被多种有丝分裂原瞬时激活，包括胰岛素、表皮生长因子和佛波酯1，2。在体外，MAP激酶将磷酸化并重新激活之前被磷酸酶处理失活的S6激酶II 3。因为许多激活MAP激酶的刺激物也是细胞增殖的刺激物，并且细胞周期的调节似乎涉及蛋白激酶的网络，所以MAP激酶在刺激物的传递中可能是重要的，最终导致细胞周期中从GO进展到G1。活化的MAP激酶含有磷酸酪氨酸和磷酸苏氨酸4。我们在这里报告，MAP激酶可以完全失活治疗与磷酸酶2A，磷酸丝氨酸和磷酸苏氨酸特异性蛋白磷酸酶，或CD 45，磷酸酪氨酸特异性蛋白磷酸酶。我们证明，MAP激酶是唯一的活性时，酪氨酰和苏氨酰残基被磷酸化，并建议因此，酶的功能在体内整合来自两个不同的转导途径的信号。
MAP kinase (relative molecular mass, 42,000), a low abundance serine-threonine protein kinase, is transiently activated in many cell types by a variety of mitogens, including insulin, epidermal growth factor, and phorbol esters1,2. In vitro, MAP kinase will phosphorylate and reactivate S6 kinase II previously inactivated by phosphatase treatment3. Because many of the stimuli that activate MAP kinase are also stimulators of cell proliferation, and regulation of the cell cycle seems to involve a network of protein kinases, MAP kinase could be important in the transmission of stimuli eventually leading to the progression from GO to Gl in the cell cycle. Activated MAP kinase contains both phosphotyrosine and phosphothreonine4. We report here that MAP kinase can be deactivated completely by treatment with either phosphatase 2A, a protein phosphatase specific for phosphoserine and phosphothreonine, or CD45, a phosphotyrosine-specific protein phosphatase. We demonstrate that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggest therefore that the enzyme functionsin vivoto integrate signals from two distinct transduction pathways.