RHO GTPases 激活 CIT
中文名称
通路描述
RHO GTPases 激活 CIT。Citron 激酶 (CIT) 或 Citron-RHO 相互作用激酶 (CRIK) 与 ROCK 激酶具有相似性。与 ROCK 类似，它由丝氨酸/苏氨酸激酶结构域、螺旋结构域、RHO 结合结构域、富含半胱氨酸的结构域和 Pleckstrin 同源结构域 (PH) 结构域组成，但此外还包含富含脯氨酸的结构域和 PDZ 结合结构域。CIT 的一种较短的剪接异构体 citron-N 在神经系统中特异性表达，且缺乏激酶结构域。Citron-N 是突触后密度 (post-synaptic density) 的组成部分，其中它与支架蛋白 PDS-95/SAP90 的 PDZ 结构域结合 (Zhang et al. 2006)。虽然 CIT 与 RHO GTPases RHOA, RHOB, RHOC 和 RAC1 的结合已得到证实 (Madaule et al. 1995)，但 CIT 由 GTP 结合的 RHO GTPases 激活的机制尚未阐明。有迹象表明，在存在活性形式的 RHO GTPases 的情况下，CIT 可能通过自磷酸化而被激活 (Di Cunto et al. 1998)。CIT 似乎将肌动蛋白调节轻链 (MRLC) 磷酸化，这是迄今为止唯一已鉴定的底物，磷酸化位点与 ROCK 磷酸化的位点相同，但尚未确定这与 RHO GTPases 激活的关系如何 (Yamashiro et al. 2003)。CIT 和 RHOA 被认为共同作用以调节高尔基体组织，通过调节细胞骨架 (Camera et al. 2003)。CIT 还参与通过与其与 KIF14 相互作用来调节胞质分裂的调控 (Gruneberg et al. 2006, Bassi et al. 2013, Watanabe et al. 2013) 以及 p27(Kip1) (Serres et al. 2012)。
英文描述
RHO GTPases activate CIT Citron kinase (CIT) or citron RHO-interacting kinase (CRIK) shares similarities with ROCK kinases. Like ROCK, it consists of a serine/threonine kinase domain, a coiled-coil region, a RHO-binding domain, a cysteine rich region and a plekstrin homology (PH) domain, but additionally features a proline-rich region and a PDZ-binding domain. A shorter splicing isoform of CIT, citron-N, is specifically expressed in the nervous system and lacks the kinase domain. Citron-N is a component of the post-synaptic density, where it binds to the PDZ domains of the scaffolding protein PDS-95/SAP90 (Zhang et al. 2006).While the binding of CIT to RHO GTPases RHOA, RHOB, RHOC and RAC1 is well established (Madaule et al. 1995), the mechanism of CIT activation by GTP-bound RHO GTPases has not been elucidated. There are indications that CIT may be activated through autophosphorylation in the presence of active forms of RHO GTPases (Di Cunto et al. 1998). CIT appears to phosphorylate the myosin regulatory light chain (MRLC), the only substrate identified to date, on the same residues that are phosphorylated by ROCKs, but it has not been established yet how this relates to activation by RHO GTPases (Yamashiro et al. 2003). CIT and RHOA are implicated to act together in Golgi apparatus organization through regulation of the actin cytoskeleton (Camera et al. 2003). CIT is also involved in the regulation of cytokinesis through its interaction with KIF14 (Gruneberg et al. 2006, Bassi et al. 2013, Watanabe et al. 2013) and p27(Kip1) (Serres et al. 2012).
所含基因
19 个基因