Kinase Subfamily ROCK

Kinase Classification: Group AGC: Family DPMK: Subfamily ROCK

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Evolution

ROCK is an animal specific kinase duplicated in vertebrates (ROCK1, ROCK2), and with homologs in Drosophila (rok) and C. elegans (let-502).

Domain Structure

ROCK kinases are long multidomain proteins of ~1300 AA. They have an N-terminal kinase domain with the AGC-specific kinase domain tail, followed by a central coiled-coil region, HR1 domain, Rho-binding, HR and PH domains. The PH domain is split by an inserted CRD (cysteine-rich Zn finger motif).

Functions

Rock is activated by the small GTPase Rho and modulates the cytoskeleton by phosphorylation of a wide array of other cytoskeletal proteins. Binding of Rho-GTP to the RBD relieves an intramolecular inhibition and activates the kinase activity.

Substrates include LIMK kinase which phosphorylates and inhibits cofilin, blocking its actin-depolymerizing function, and myosin regulatory light chain (MRLC2/MYL12B in human, sqh in Drosophila) that regulates Myosin II.

Drosophila rok is well-studied in the planar cell polarity pathway, where it is downstream of frizzled and dishevelled and phosphorylates the non-muscle myosin light chain, regulating Myosin II. It is activated by Rho1, the single homolog of human RhoA/B/C which also activate ROCK.