Platanias Leonidas C
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago IL 60611, USA.
Blood. 2003 Jun 15;101(12):4667-79. doi: 10.1182/blood-2002-12-3647. Epub 2003 Mar 6.
Mitogen-activated protein (Map) kinases are widely expressed serine-threonine kinases that mediate important regulatory signals in the cell. Three major groups of Map kinases exist: the p38 Map kinase family, the extracellular signal-regulated kinase (Erk) family, and the c-Jun NH2-terminal kinase (JNK) family. The members of the different Map kinase groups participate in the generation of various cellular responses, including gene transcription, induction of cell death or maintenance of cell survival, malignant transformation, and regulation of cell-cycle progression. Depending on the specific family isoform involved and the cellular context, Map kinase pathways can mediate signals that either promote or suppress the growth of malignant hematopoietic cells. Over the last few years, extensive work by several groups has established that Map kinase pathways play critical roles in the pathogenesis of various hematologic malignancies, providing new molecular targets for future therapeutic approaches. In this review, the involvement of various Map kinase pathways in the pathophysiology of hematologic malignances is summarized and the clinical implications of the recent advances in the field are discussed.
丝裂原活化蛋白(Map)激酶是广泛表达的丝氨酸 - 苏氨酸激酶,可介导细胞内重要的调节信号。存在三大类Map激酶:p38 Map激酶家族、细胞外信号调节激酶(Erk)家族和c - Jun氨基末端激酶(JNK)家族。不同Map激酶组的成员参与各种细胞反应的产生,包括基因转录、诱导细胞死亡或维持细胞存活、恶性转化以及细胞周期进程的调节。根据所涉及的特定家族异构体和细胞环境,Map激酶途径可介导促进或抑制恶性造血细胞生长的信号。在过去几年中,多个研究小组的大量工作证实,Map激酶途径在各种血液系统恶性肿瘤的发病机制中起关键作用,为未来的治疗方法提供了新的分子靶点。在本综述中,总结了各种Map激酶途径在血液系统恶性肿瘤病理生理学中的参与情况,并讨论了该领域最新进展的临床意义。