ROCK

Rho-associated coiled-coil containing kinases (ROCK) were originally identified as effectors of the RhoA small GTPase. In humans, ROCK1 and ROCK2 both contain 33 exons and are located on chromosome 18 (18q11.1) and 2 (2p24) respectively. The ROCK1 open reading frame encodes 1354 amino acids, whereas ROCK2 encodes 1388 amino acids. ROCK2 also has a reported splice variant, preferentially expressed in skeletal muscle, which results in the inclusion of 57 additional amino acids. The kinase domains of ROCK are closely related to many homologous domains in this family, including dystrophia myotonica protein kinase (DMPK), myotonic dystrophy kinase related-Cdc42 related kinases (MRCK) α and β, and citron Rho-interacting kinase (CRIK). To date, the crystal structures of the kinase domains from ROCK1,8 ROCK2,9 MRCKβ,10 and DMPK11 have been determined, which has highlighted the high degree of tertiary as well as primary similarity. N-terminal and carboxyl-terminal extensions of the ROCK kinase domains are essential for catalytic activity. 
ROCK1 and ROCK2 play distinct roles in the subcellular sites of MLC phosphorylation and in the assembly of fibronectin matrices at the cell surface during actin cytoskeleton mediated extracellular matrix assembly.  ROCK1 regulates peripheral actomyosin ring formation through MLC phosphorylation and ROCK2 stabilizes the cytoskeleton through cofilin phosphorylation following treatment with the chemotherapeutic drug doxorubicin.  ROCK1 and ROCK2 may have different functions in cells, likely due to differences in the way that there are regulated and subtle differences in localization that result from non-overlapping patterns of protein binding. During the apoptosis execution phase, caspase-3 cleaves ROCK1 to remove the auto-inhibitory C-terminal domain, which results in constitutive ROCK1 activation and subsequent induction of plasma membrane blebbing through MLC phosphorylation and ensuing contractile force generation. The importance of ROCK1 for apoptotic blebbing has been shown in numerous additional cell types, including cardiac myocytes, lymphoma cells, and non-small cell lung carcinoma cells. ROCK may also have a general positive role as a promoter of cell proliferation in many cell types, with some exceptions in specialized contexts.

References

1.Julian L,et al.Small GTPases. 2014;5:e29846.