Rock1
Domain
The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated.
Function
Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:19036714, PubMed:19181962). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (PubMed:19036714, PubMed:19181962). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (By similarity). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (PubMed:20008297). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (PubMed:30115939). Promotes keratinocyte terminal differentiation (By similarity). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (PubMed:21768292). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (PubMed:15753128).
Post-translational modifications
Autophosphorylated on serine and threonine residues.
Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing (By similarity).
Sequence Similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Tissue Specificity
Highly expressed in brain, heart, lung, liver, stomach, spleen, kidney, testis, muscle, embryo and placenta.
Cellular localization
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Centriole
- Golgi apparatus membrane
- Peripheral membrane protein
- Cell projection
- Bleb
- Cytoplasm
- Cytoskeleton
- Cell membrane
- Cell projection
- Lamellipodium
- Cell projection
- Ruffle
- A small proportion is associated with Golgi membranes (By similarity). Associated with the mother centriole and an intercentriolar linker (PubMed:16741948). Colocalizes with ITGB1BP1 and ITGB1 at the cell membrane predominantly in lamellipodia and membrane ruffles, but also in retraction fibers (PubMed:16741948). Localizes at the cell membrane in an ITGB1BP1-dependent manner (PubMed:16741948).
Alternative names
Rho-associated protein kinase 1, p160 ROCK-1, ROCK-I, p160ROCK