RHO GTPases activate CIT

Stable Identifier
R-HSA-5625900
Type
Pathway
Species
Homo sapiens
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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
PubMed ID Title Journal Year
16202622 Targeting and clustering citron to synapses

Benson, DL, Zhang, W

Mol. Cell. Neurosci. 2006
23716662 Citron kinase controls a molecular network required for midbody formation in cytokinesis

Bassi, ZI, D'Avino, PP, Riparbelli, MG, Audusseau, M, Callaini, G

Proc. Natl. Acad. Sci. U.S.A. 2013
9792683 Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron

Calautti, E, Turco, E, Di Cunto, F, Ong, L, Dotto, GP, Topley, G, Hsiao, J

J. Biol. Chem. 1998
8543060 A novel partner for the GTP-bound forms of rho and rac

Madaule, P, Narumiya, S, Furuyashiki, T, Watanabe, G, Reid, T, Ishizaki, T, Morii, N

FEBS Lett. 1995
22293177 p27(Kip1) controls cytokinesis via the regulation of citron kinase activation

Serres, MP, Besson, A, Chi, Y, Kossatz, U, Malek, NP, Roberts, JM

J. Clin. Invest. 2012
12802051 Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II

Narumiya, S, Sasaki, Y, Totsukawa, G, Matsumura, F, Yamashiro, S, Ishizaki, T, Madaule, P, Yamakita, Y

Mol. Biol. Cell 2003
16431929 KIF14 and citron kinase act together to promote efficient cytokinesis

Chalamalasetty, RB, Neef, R, Barr, FA, Nigg, EA, Chan, EH, Gruneberg, U, Li, X

J. Cell Biol. 2006
23444367 Citron kinase mediates transition from constriction to abscission through its coiled-coil domain

Narumiya, S, Ishizaki, T, De Zan, T, Watanabe, S

J. Cell. Sci. 2013
14595335 Citron-N is a neuronal Rho-associated protein involved in Golgi organization through actin cytoskeleton regulation

Di Cunto, F, Imarisio, S, Ferrara, L, Camera, P, da Silva, JS, Schubert, V, Griffiths, G, Dotti, CG, Silengo, L, Giuffrida, MG

Nat. Cell Biol. 2003
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