丝裂原活化蛋白激酶在心脏发育和疾病中的作用
Mitogen-activated protein kinases in heart development and diseases.
作者信息
Wang Yibin
机构信息
Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
出版信息
Circulation. 2007 Sep 18;116(12):1413-23. doi: 10.1161/CIRCULATIONAHA.106.679589.
Abstract
Mitogen-activated protein (MAP) kinases belong to a highly conserved family of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological functions. The 4 best-characterized MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, have been implicated in different aspects of cardiac regulation, from development to pathological remodeling. Recent advancements in the development of kinase-specific inhibitors and genetically engineered animal models have revealed significant new insights about MAP kinase pathways in the heart. However, this explosive body of new information also has yielded many controversies about the functional role of specific MAP kinases as either detrimental promoters or critical protectors of the heart during cardiac pathological processes. These uncertainties have raised questions on whether/how MAP kinases can be targeted to develop effective therapies against heart diseases. In this review, recent studies examining the role of MAP kinase subfamilies in cardiac development, hypertrophy, and survival are summarized.
摘要
丝裂原活化蛋白（MAP）激酶属于人类激酶组中高度保守的丝氨酸 - 苏氨酸蛋白激酶家族，在广泛的生理功能中具有多种作用。4条特征最明确的MAP激酶途径，即ERK1/2、JNK、p38和ERK5，已被证明参与心脏调节的不同方面，从心脏发育到病理重塑。激酶特异性抑制剂和基因工程动物模型开发方面的最新进展揭示了关于心脏中MAP激酶途径的重要新见解。然而，这大量的新信息也引发了许多关于特定MAP激酶在心脏病理过程中作为心脏有害促进因子或关键保护因子的功能作用的争议。这些不确定性引发了关于是否/如何靶向MAP激酶以开发有效心脏病治疗方法的问题。在本综述中，总结了近期研究MAP激酶亚家族在心脏发育、肥大和存活中的作用。
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