cd20875

protein kinase C conserved region 1 (C1 domain) found in Rho-associated coiled-coil containing protein kinase 2 (ROCK2) and similar proteins

CDD entry
Member databaseCDD
CDD typedomain
Short nameC1_ROCK2
SetC1

Description

ROCK2 is a serine/threonine kinase, catalyzing the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2, also called Rho-associated protein kinase 2, Rho kinase 2, Rho-associated, coiled-coil-containing protein kinase II (ROCK-II), or p164 ROCK-2, was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK proteins contain an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD), a pleckstrin homology (PH) domain and a C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.
[5, 15, 12, 14, 13, 3, 11, 17, 10, 16, 8, 1, 7, 4, 6, 9, 2]

References

1.RhoA/Rho-kinase in erectile tissue: mechanisms of disease and therapeutic insights. Jin L, Burnett AL. Clin Sci (Lond) 110, 153-65, (2006). PMID: 16411892

2.Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil. Yamaguchi H, Kasa M, Amano M, Kaibuchi K, Hakoshima T. Structure 14, 589-600, (2006). View articlePMID: 16531242

3.RhoA/Rho-kinase pathway: much more than just a modulation of vascular tone. Evidence from studies in humans. Calo LA, Pessina AC. J Hypertens 25, 259-64, (2007). PMID: 17211228

4.Development of specific Rho-kinase inhibitors and their clinical application. Tamura M, Nakao H, Yoshizaki H, Shiratsuchi M, Shigyo H, Yamada H, Ozawa T, Totsuka J, Hidaka H. Biochim Biophys Acta 1754, 245-52, (2005). PMID: 16213195

5.Vascular rho kinases and their potential therapeutic applications. Budzyn K, Sobey CG. Curr Opin Drug Discov Devel 10, 590-6, (2007). PMID: 17786858

6.Rho kinase, a promising drug target for neurological disorders. Mueller BK, Mack H, Teusch N. 4, 387-98, (2005). View articlePMID: 15864268

7.Rho/Rho-kinase and C-reactive protein relationship in hypertension and atherosclerosis. Calo LA, Pagnin E, Mussap M, Davis PA, Semplicini A. Nephrol Dial Transplant 21, 1131-2, (2006). PMID: 16287911

8.Rho/Rho kinase as a potential target for the treatment of renal disease. Wakino S, Kanda T, Hayashi K. Drug News Perspect 18, 639-43, (2005). PMID: 16491166

9.The ups and downs of Rho-kinase and penile erection: upstream regulators and downstream substrates of rho-kinase and their potential role in the erectile response. Chitaley K, Webb RC, Mills TM. Int J Impot Res 15, 105-9, (2003). PMID: 12789389

10.Dependence of proliferating dedifferentiated vascular smooth muscle contraction on Rho-Rho kinase system. Nishimura J, Bi D, Kanaide H. Trends Cardiovasc Med 16, 124-8, (2006). PMID: 16713535

11.Rho kinase: a target for treating urinary bladder dysfunction? Peters SL, Schmidt M, Michel MC. Trends Pharmacol Sci 27, 492-7, (2006). PMID: 16870270

12.Development of Rho-kinase inhibitors for cardiovascular medicine. Shimokawa H, Rashid M. Trends Pharmacol Sci 28, 296-302, (2007). PMID: 17482681

13.Progress of the study of rho-kinase and future perspective of the inhibitor. Tawara S, Shimokawa H. Yakugaku Zasshi 127, 501-14, (2007). PMID: 17329936

14.Rho kinase in the regulation of cell death and survival. Shi J, Wei L. Arch Immunol Ther Exp (Warsz) 55, 61-75, (2007). PMID: 17347801

15.Rho GTPase/Rho kinase inhibition as a novel target for the treatment of glaucoma. Rao VP, Epstein DL. BioDrugs 21, 167-77, (2007). PMID: 17516712

16.Rho-kinase as a drug target for the treatment of airway hyperrespon-siveness in asthma. Gosens R, Schaafsma D, Nelemans SA, Halayko AJ. Mini Rev Med Chem 6, 339-48, (2006). PMID: 16515473

17.Recent evidence for an involvement of rho-kinase in cerebral vascular disease. Chrissobolis S, Sobey CG. Stroke 37, 2174-80, (2006). PMID: 16809566

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