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Concept
Rho-associated protein kinase
Résumé
Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton.
ROCKs (ROCK1 and ROCK2) occur in mammals (human, rat, mouse, cow), zebrafish, Xenopus, invertebrates (C. elegans, mosquito, Drosophila) and chicken. Human ROCK1 has a molecular mass of 158 kDa and is a major downstream effector of the small GTPase RhoA. Mammalian ROCK consists of a kinase domain, a coiled-coil region and a Pleckstrin homology (PH) domain, which reduces the kinase activity of ROCKs by an autoinhibitory intramolecular fold if RhoA-GTP is not present.
Rat ROCKs were discovered as the first effectors of Rho and they induce the formation of stress fibers and focal adhesions by phosphorylating MLC (myosin light chain).
Due to this phosphorylation, the actin binding of myosin II and, thus, the contractility increases. Two mouse ROCK isoforms ROCK1 and ROCK2 have been identified. ROCK1 is mainly expressed in the lung, liver, spleen, kidney and testis. However, ROCK2 is distributed mostly in the brain and heart.
Protein kinase C and Rho-associated protein kinase are involved in regulating calcium ion intake; these calcium ions, in turn stimulate a myosin light chain kinase, forcing a contraction. Rho-associated protein kinase are serine or threonine kinases that determine the calcium sensitivity in smooth muscle cells.
ROCK plays a role in a wide range of different cellular phenomena, as ROCK is a downstream effector protein of the small GTPase Rho, which is one of the major regulators of the cytoskeleton.
- ROCK is a key regulator of actin organization and thus a regulator of cell migration as follows: Different substrates can be phosphorylated by ROCKs, including LIM kinase, myosin light chain (MLC) and MLC phosphatase.
Source officielle
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