Schäfer C, Williams J A
Department of Physiology 7737 Medical Science II, University of Michigan, Ann Arbor, 48109-0622, USA.
J Gastroenterol. 2000;35(1):1-9. doi: 10.1080/003655200750024443.
Mitogen-activated protein kinases (MAPKs) and heat shock proteins (Hsps) are ubiquitous proteins that function in both normal and stress-related pathophysiological states of the cell. Recent advances in the study of such Hsps and their interaction with signaling kinase cascades, including the cloning of new members, has helped to define their physiological roles in various tissues. In the pancreas, three major MAPKs, ERKs, JNKs, and p38, have been demonstrated. While intracellular signals involved in the ERK cascade have been most extensively investigated, only a few upstream regulators and downstream effector proteins of the JNKs and p38 MAPK are known in the pancreas. Similarly, a number of Hsps have been identified in pancreas, including Hsp27, Hsp60, and Hsp70. Although the activation of various MAPKs and the induction of Hsp expression have clearly been demonstrated following experimental exposure of rodent pancreas to stress conditions, it remains to be determined whether Hsps have a protective or detrimental effect during acute pancreatitis or at the onset of pancreatic carcinoma. This review will summarize current knowledge of the regulation and function of stress-activated kinases and stress proteins in the pancreas.
丝裂原活化蛋白激酶（MAPKs）和热休克蛋白（Hsps）是普遍存在的蛋白质，在细胞的正常和应激相关病理生理状态中均发挥作用。此类热休克蛋白及其与信号激酶级联反应相互作用的研究取得了新进展，包括新成员的克隆，这有助于明确它们在各种组织中的生理作用。在胰腺中，已证实存在三种主要的丝裂原活化蛋白激酶，即细胞外信号调节激酶（ERKs）、应激活化蛋白激酶（JNKs）和p38。虽然对细胞外信号调节激酶级联反应所涉及的细胞内信号进行了最广泛的研究，但在胰腺中，已知的应激活化蛋白激酶和p38丝裂原活化蛋白激酶的上游调节因子和下游效应蛋白却很少。同样，在胰腺中已鉴定出多种热休克蛋白，包括热休克蛋白27（Hsp27）、热休克蛋白60（Hsp60）和热休克蛋白70（Hsp70）。尽管在将啮齿动物胰腺实验性暴露于应激条件后，已明确证实了各种丝裂原活化蛋白激酶的激活和热休克蛋白表达的诱导，但热休克蛋白在急性胰腺炎期间或胰腺癌发病时是具有保护作用还是有害作用仍有待确定。本综述将总结目前关于胰腺中应激激活激酶和应激蛋白的调节及功能的知识。
