Rho-kinase: regulation, (dys)function, and inhibition.
In a variety of normal and pathological cell types, Rho-kinases I and II (ROCKI/II) play a pivotal role in the organization of the nonmuscle and smooth muscle cytoskeleton and adhesion plaques as well as in the regulation of transcription factors. Thus, ROCKI/II activity regulates cellular contraction, motility, morphology, polarity, cell division, and gene expression. Emerging evidence suggests that dysregulation of the Rho-ROCK pathways at different stages is linked to cardiovascular, metabolic, and neurodegenerative diseases as well as cancer. This review focuses on the current status of understanding the multiple functions of Rho-ROCK signaling pathways and various modes of regulation of Rho-ROCK activity, thereby orchestrating a concerted functional response.
Ehsan
E
Amin
Badri Nath
BN
Dubey
Si-Cai
SC
Zhang
Lothar
L
Gremer
Radovan
R
Dvorsky
Jens M
JM
Moll
Mohamed S
MS
Taha
Luitgard
L
Nagel-Steger
Roland P
RP
Piekorz
Avril V
AV
Somlyo
Mohammad R
MR
Ahmadian
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D055550:Protein Stability; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology; D020743:rhoB GTP-Binding Protein / Q000502:physiology; D000075024:rhoC GTP-Binding Protein
C066737:RHOA protein, human; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein