Reactome: A Curated Pathway Database

RHO GTPases activate CIT

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

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).

Literature References
Participant Of
Orthologous Events
Cross References
BioModels Database