Difference between revisions of "Kinase Subfamily ROCK"
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[[kinase classification|Kinase Classification]]: [[Kinase_Group_AGC|Group AGC]]: [[Kinase_Family_DPMK|Family DPMK]]: [[Kinase_Subfamily_ROCK|Subfamily ROCK]] | [[kinase classification|Kinase Classification]]: [[Kinase_Group_AGC|Group AGC]]: [[Kinase_Family_DPMK|Family DPMK]]: [[Kinase_Subfamily_ROCK|Subfamily ROCK]] | ||
| − | + | ROCK subfamily kinases modulate the cytoskeleton in response to Rho GTPase signaling. | |
====Evolution==== | ====Evolution==== | ||
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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. | 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 [[Kinase_Subfamily_LIMK|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. | + | Substrates include [[Kinase_Subfamily_LIMK|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. MRLC is also activated by the [[Kinase_Subfamily_DRAK|DRAK]] kinase <cite> Neubuesser</cite>. |
| − | 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. | + | Drosophila rok is well-studied in the planar cell polarity pathway, where it is genetically downstream of frizzled and dishevelled and phosphorylates the non-muscle myosin light chain, regulating Myosin II <cite>Winter</cite>. It is activated by Rho1, the single homolog of human RhoA/B/C which also activate ROCK. |
====References==== | ====References==== | ||
| + | <biblio> | ||
| + | #Winter pmid=11301004 | ||
| + | #Neubuesser pmid=20573980 | ||
| + | </biblio> | ||
Revision as of 20:11, 16 March 2023
Kinase Classification: Group AGC: Family DPMK: Subfamily ROCK
ROCK subfamily kinases modulate the cytoskeleton in response to Rho GTPase signaling.
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. MRLC is also activated by the DRAK kinase [1].
Drosophila rok is well-studied in the planar cell polarity pathway, where it is genetically downstream of frizzled and dishevelled and phosphorylates the non-muscle myosin light chain, regulating Myosin II [2]. It is activated by Rho1, the single homolog of human RhoA/B/C which also activate ROCK.
References
- Neubueser D and Hipfner DR. Overlapping roles of Drosophila Drak and Rok kinases in epithelial tissue morphogenesis. Mol Biol Cell. 2010 Aug 15;21(16):2869-79. DOI:10.1091/mbc.E10-04-0328 |
- Winter CG, Wang B, Ballew A, Royou A, Karess R, Axelrod JD, and Luo L. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell. 2001 Apr 6;105(1):81-91. DOI:10.1016/s0092-8674(01)00298-7 |
