Rho-associated protein kinase 2; Rho kinase 2; Rho-associated, coiled-coil-containing protein kinase 2; p164 ROCK-2 (ROCK2, KIAA0619)

Function

• regulates assembly of actin cytoskeleton & cell polarity
• role in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber & focal adhesion formation, neurite retraction, cell adhesion & cell motility
• phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A & VIM
• phosphorylates SORL1 & IRF4
• negative regulator of VEGF-induced angiogenic endothelial cell activation
• positively regulates the activation of p42/MAPK1-p44/MAPK3 & of p90RSK/RPS6KA1 during myogenic differentiation.
• role in initiation of centrosome duplication
• inhibits keratinocyte terminal differentiation
• may regulate closure of the eyelids & ventral body wall through organization of actomyosin bundles
• role in the regulation of synaptic spines in hippocampus
• role in generating the circadian rhythm of aortic myofilament Ca+2 sensitivity & vascular contractility by modulating the myosin ight chain phosphorylation
• phosphorylated upon DNA damage, probably by ATM or ATR
• activated by RHOA binding
  • binds RHOA that has been activated by GTP binding
• phosphorylation at Tyr-722 reduces its binding to RHOA & is crucial for focal adhesion dynamics
• dephosphorylation by PTPN11 stimulates its RHOA binding activity
• cleaved by granzyme B during apoptosis, leading to constitutive activation of the kinase & membrane blebbing
• interacts with CHORDC1, RAF1, PPP1R12A, SORL1, EP300 & BRCA2
• interacts with NPM1
• binds IRS1, RHOB & RHOC
• not cleaved by caspase 3
• inhibited by Y-27632

Cofactor: Mg+2 (putative)

Structure

• homodimer
• belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family
• contains 1 AGC-kinase C-terminal domain
• contains 1 PH domain
• contains 1 phorbol-ester/DAG-type Zn+2 finger
• contains 1 protein kinase domain
• contains 1 REM (Hr1) repeat
• interaction between Thr-414 & Asp-48 is essential for kinase activity & dimerization
• unlike ROCK1, does not contain caspase 3 consensus sequence in C-terminal

Compartment

• cytoplasm (putative)
• cell membrane
• nucleus. cytoplasm, cytoskeleton, microtubule organizing center, centrosome
• cytoplasmic, & associated with actin microfilaments & the plasma membrane

Comparative biology

• IL-17 facilitates Rho-kinase dependent inhibitory phosphorylation of endothelial nitric oxide synthase in mice reducing nitric oxide production in cerebral endothelial cells, inhibiting resting cerebral perfusion & endothelial function, leading to cognitive impairment*

* not clear if this is ROCK1, ROCK2 or both

More general terms

• rho-associated kinase ROCK
• zinc finger protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9475
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9475
• OMIM: https://mirror.omim.org/entry/604002
• UniProt: http://www.uniprot.org/uniprot/O75116.html