Activation of membrane protein-tyrosine phosphatase involving cAMP- and Ca2+/phospholipid-dependent protein kinases.
Activation of membrane protein-tyrosine phosphatase involving cAMP- and Ca2+/phospholipid-dependent protein kinases.
复制标题
膜蛋白酪氨酸磷酸酶的激活涉及 cAMP 和 Ca2/磷脂依赖性蛋白激酶。
DOI：
10.1073/pnas.88.15.6696
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发表时间：
1991
影响因子：
11.1
通讯作者：
F. Pinault
中科院分区：
文献类型：
--
作者：
D. Brautigan;F. Pinault
信号转导的关键是“串扰”机制，以协调不同的途径。本研究表明，刺激丝氨酸/苏氨酸蛋白激酶可激活蛋白酪氨酸磷酸酶(PTPase；蛋白酪氨酸磷酸水解酶，EC 3.1.3.48)。胞内95%以上的PTPase存在于不同细胞系的颗粒组分中，并被洗涤剂提取为含有55 kDa催化亚基的150 kDa的复合体。该复合体被蛋白酶消化激活，从而改变了其底物专一性，与尺寸减小一致。用3M溴化锂处理膜部分，使络合物解离。用异丙肾上腺素、Forskolin或cAMP类似物刺激cAMP依赖的蛋白激酶(PKA)，或用佛波酯或二辛酰甘油刺激钙/磷脂依赖的蛋白激酶(PKC)，可使膜PTPase复合体激活，但其大小不变。用冈田酸或氟化物抑制蛋白-丝氨酸/苏氨酸磷酸酶也会导致膜PTPase的激活。这些结果支持了一个模型，通过磷酸化和去磷酸化与55-kDa PTPase催化亚基复合的调节成分中的丝氨酸/苏氨酸残基来调节PTPase。这一机制可能在调节通过酪氨酸磷酸化转导的细胞外信号的敏感性以及细胞周期中事件的同步性方面发挥重要作用。
Essential to signal transduction are mechanisms of "cross-talk" to coordinate different pathways. This study shows that stimulation of serine/threonine protein kinases activates protein-tyrosine phosphatase (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48). More than 95% of intracellular PTPase was in the particulate fraction of various cell lines and was extracted with detergent as a 150-kDa complex that contained a 55-kDa catalytic subunit. The complex was activated by protease digestion, which changed its substrate specificity coincident with reduction in size. The complex was dissociated by treatment of the membrane fraction with 3 M LiBr. Treatment of intact cells with isoproterenol, forskolin, or cAMP analogues to stimulate cAMP-dependent protein kinase (PKA) or with phorbol ester or dioctanoylglycerol to stimulate Ca2+/phospholipid-dependent protein kinase (PKC) produced activation of membrane PTPase complex without a change in its size. Inhibition of protein-serine/threonine phosphatases with okadaic acid or fluoride also resulted in activation of the membrane PTPase. These results support a model for regulation of PTPase by phosphorylation and dephosphorylation of serine/threonine residues in a regulatory component complexed with the 55-kDa PTPase catalytic subunit. This mechanism may be important in regulating sensitivity to extracellular signals transduced via tyrosine phosphorylation and in the synchronization of events during the cell cycle.