MRCK与cdc42的一些资料.docVIP

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MRCK与cdc42的一些资料

关于MRCKbata 和 Cdc42两者之间关系(来自丁香通): Protein kinases comprise a large group of encoded factors that regulate cellular processes by catalyzing the transfer of a phosphate group to a hydroxyl(羟基,氢氧基) acceptor in serine, threonine or tyrosine residues. Myotonic dystrophy kinaserelated Cdc42-binding (DMPK-like) kinases-α and β (MRCK-α, β) contain a cysteine-rich motif and a putative pleckstrin homology domain. MRCKs can phosphorylate nonmuscle Myosin light chain and influences Actin-Myosin contractility(收缩性,伸缩力). MRCK-α can phosphorylate and activate LIM kinases downstream of Cdc42, which leads to inactivation of ADF/Cofilin and to Actin cytoskeletal reorganization. MRCK-α can also influence neurite outgrowth promoted by Cdc42 and Rac. Myotonic Dystrophy(肌强制性营养不良) Kinase-Related cdc42-binding kinase beta (MRCKb) belongs to the DMPK subfamily. The myotonic dystrophy kinase-related kinases and myotonic dystrophy kinase-related Cdc42 binding kinase (MRCK) are effectors of RhoA and Cdc42, respectively, where they are involved in actin cytoskeletal reorganization and neurite(神经突) outgrowth. Effects of the repeat expansion on the DMPK gene may be responsible for muscle and heart features of Myotonic Dystrophy. Characterization of a monoclonal antibody panel shows that the myotonic dystrophy protein kinase, DMPK, is expressed almost exclusively in muscle and heart. Hum. Mol. Genet. 9 , 2167-2173, (2000) Abstract Tan, I. et al., Phosphorylation of a novel myosin binding subunit of protein phosphatase 1 reveals a conserved mechanism in the regulation of actin cytoskeleton. J. Biol. Chem. 276 , 21209-21216, (2001) Abstract 细胞体前移的过程受到小Rho GTP酶Cdc42, Rac和RhoA的调控。而这些蛋白相互之间却是拮抗的关系。RhoA 激活Rho-激酶(又名ROCK),后者在激活状态下会将肌球蛋白轻链磷酸酶(myosin light chain phosphatase,简称MLC磷酸酶。该酶为MLC去掉磷酸基团)磷酸化,就是使它失活了,导致细胞的收缩增强。Cdc42也是通过MRCK起到类似的作用。与它们相反的是,Rac会激活PAK,PAK能磷酸化MLC激酶,使之失活,后果是细胞收缩力减退,扩展受阻。但是PAK也能直接磷酸化MLC,增加细胞收缩能力。究竟是哪种作用占优,取决于PAK的空间分布和它的活性调节水平 在肌球蛋白介导的胞体收缩过程中,RhoA和Rac通过Rho-激酶和PAK可以调节MLC的磷酸化,这也为尾部粘着斑解聚做出贡

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