Disease relevance of ROCK2

• The results suggest that common variation in ROCK2 exerts systemic resistance-mediated changes in BP, documenting a novel mechanism for human circulatory control, and suggesting new possibilities for diagnostic profiling and treatment of subjects at risk of developing hypertension [1].

High impact information on ROCK2

• We demonstrate that macrophage adherence promotes rapid changes in physiological functions that depend on translational upregulation of preformed ROCK-1 mRNA, but not ROCK-2 mRNA [2].
• Upon binding to RhoA, ROCK-2 becomes autophosphorylated and demonstrates stimulated kinase activity [3].
• Our analysis indicates that the ribozymes toward ROCK1 can block invasive activity but not the proliferation of HT1080 cells without having any effect on expression of ROCK2 [4].
• These observations suggest that nucleus-localized ROCK2 targets p300 for phosphorylation to regulate its acetyltransferase activity [5].
• Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown [6].

Biological context of ROCK2

• Common genetic variation (Thr431Asn) at ROCK2 predicts increased BP, systemic vascular resistance (although not large artery compliance), and resistance in response to the endogenous renin-angiotensin system, indicating a resistance vessel-based effect on elevated BP [1].
• The Asn/Asn genotype (compared with Asn/Thr or Thr/Thr) was associated with greater resting systolic (P<0.001), diastolic (P<0.0001), and mean BP (P<0.0001); allelic variation at ROCK2 accounted for up to approximately 5% of BP variation (P<0.0001) [1].

Anatomical context of ROCK2

• That this is of importance is supported by the findings that an increased Rho-kinase/ROCK activity in SW13 cells, obtained by overexpressing wild-type ROCK1 and ROCK2, induces stress-fibre formation [7].
• Taken together, our results demonstrate that the expression and activity of ROCK1 and ROCK2 can be uncoupled in a signal-dependent manner, and further implicate a new function for ROCK2 in the steroid control of tight junction dynamics [8].
• In this study, first of all we investigated the expression of Rho-kinase (ROCK-2) and then the role of this protein in the control of smooth muscle contraction in the isolated human gallbladder [9].

Other interactions of ROCK2

• The small G protein RhoA and its downstream effector Rho-kinase/ROCK2 play an important role in regulation of various vasculature cellular functions [10].

Analytical, diagnostic and therapeutic context of ROCK2

• However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible [6].
• Nuclear ROCK2 is present in a large protein complex and partially cofractionates with p300 by gel filtration analysis [5].
• By immunofluorescence, ROCK2 partially colocalizes with p300 in distinct insoluble nuclear structures [5].

References