Andersson M B, Ketterman A J, Bogoyevitch M A
William Harvey Research Institute, Charterhouse Square, London, EC1M 6BQ, England.
Biochem Biophys Res Commun. 1998 Oct 9;251(1):328-33. doi: 10.1006/bbrc.1998.9476.
Previous studies have suggested that the contribution of inducible phosphatases to ERK MAPK deactivation is both cell-type- and agonist-specific. The aim of this study was to define the role of inducible phosphatases in ERK MAPK regulation in cardiac myocytes. We examined the kinetics of activation/deactivation of ERK MAPKs following the exposure of cardiac myocytes to endothelin-1 or phorbol ester. Deactivation was prevented by inhibition of protein synthesis indicating a contribution of inducible phosphatases. In contrast, okadaic acid failed to prolong ERK MAPK activation, but activated three myelin basic protein kinases (MBPKs, 55, 62, and 87 kDa) and two c-Jun kinases (46 and 55 kDa). Although the identity of the MBPKs is unknown, the c-Jun kinases corresponded to JNK MAPKs. Simultaneous exposure of cardiac myocytes to okadaic acid and osmotic shock potentiated JNK MAPK activation. Thus, inducible phosphatases regulate ERK MAPK deactivation, whereas okadaic acid-sensitive phosphatases regulate JNK MAPKs and three novel MBPKs.
以往的研究表明，诱导性磷酸酶对ERK丝裂原活化蛋白激酶（MAPK）失活的作用具有细胞类型和激动剂特异性。本研究的目的是确定诱导性磷酸酶在心肌细胞中ERK MAPK调节中的作用。我们检测了心肌细胞暴露于内皮素-1或佛波酯后ERK MAPK激活/失活的动力学。通过抑制蛋白质合成可阻止失活，这表明诱导性磷酸酶发挥了作用。相反，冈田酸未能延长ERK MAPK的激活时间，但激活了三种髓鞘碱性蛋白激酶（MBPKs，55、62和87 kDa）和两种c-Jun激酶（46和55 kDa）。虽然MBPKs的身份尚不清楚，但c-Jun激酶对应于JNK MAPKs。心肌细胞同时暴露于冈田酸和渗透压休克可增强JNK MAPK的激活。因此，诱导性磷酸酶调节ERK MAPK的失活，而冈田酸敏感的磷酸酶调节JNK MAPKs和三种新的MBPKs。
