Byon J C, Dadke S S, Rulli S, Kusari A B, Kusari J
Department of Physiology, Tulane University School of Medicine, New Orleans, LA, USA.
Mol Cell Biochem. 2001 Feb;218(1-2):131-8. doi: 10.1023/a:1007204508882.
Previously, we have reported that insulin induces the expression of the dual-specificity tyrosine phosphatase Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) and that this may represent a negative feedback mechanism to regulate insulin-stimulated MAP kinase activity. In this work, the mechanism of regulation of MKP-1 expression by insulin was examined, particularly the role of the MAP kinase superfamily. Inhibition of the ERK pathway attenuated insulin-stimulated MKP-1 mRNA expression. Expression of dominant negative molecules of the JNK pathway also abolished insulin-stimulated MKP-1 expression. However, inhibition of p38MAPK activity by SB202190 had no effect on insulin-stimulated MKP-1 induction. Simultaneous inhibition of the ERK and JNK pathways abolished the ability of insulin to stimulate MKP-1 expression, however, this combined inhibition was neither additive nor synergistic, suggesting these pathways converge to act on a common final effector. In conclusion, induction of MKP-1 mRNA expression in Hirc B cells by insulin requires activation of both the ERK and JNK pathways, but not p38MAPK.
此前，我们曾报道胰岛素可诱导双特异性酪氨酸磷酸酶丝裂原活化蛋白（MAP）激酶磷酸酶-1（MKP-1）的表达，这可能代表一种负反馈机制，用于调节胰岛素刺激的MAP激酶活性。在本研究中，我们检测了胰岛素调节MKP-1表达的机制，特别是MAP激酶超家族的作用。抑制ERK途径可减弱胰岛素刺激的MKP-1 mRNA表达。JNK途径显性负性分子的表达也消除了胰岛素刺激的MKP-1表达。然而，SB202190抑制p38MAPK活性对胰岛素刺激的MKP-1诱导没有影响。同时抑制ERK和JNK途径消除了胰岛素刺激MKP-1表达的能力，然而，这种联合抑制既没有相加作用也没有协同作用，表明这些途径汇聚作用于一个共同的最终效应器。总之，胰岛素诱导Hirc B细胞中MKP-1 mRNA表达需要ERK和JNK途径的激活，但不需要p38MAPK。
