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The two mouse ROCK isoforms, ROCK1 and ROCK2, have high homology.They have 65% amino acid sequences in common and 92% homology within their kinase domains. [1] [4]ROCKs are homologous to other metazoan kinases such as myotonic dystrophy kinase (), DMPK-related cell division control protein 42 ()-binding kinases (MRCK) and citron kinase.
RhoA and Rho kinase mechanisms have been linked to diabetes due to the up-regulated expression of targets within type 1 and 2 diabetic animals. Inhibition of this pathway prevented and ameliorated pathologic changes in diabetic complications, indicating that RhoA pathway is a promising target for therapeutic development in diabetes treatment [68]
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily.The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants.
The ROCK1 structure is a serine/threonine kinase with molecular weight of 158 kDa. [7] It is a homodimer composed of a catalytic kinase domain (residues76-338) [11] located at the amino or N-terminus of the protein, a coiled-coil region (residues 425-1100) [11] containing the Rho-binding domain, and a pleckstrin-homology domain (residues 1118-1317) [11] with a cysteine-rich domain.
A number of Rho kinase inhibitors are known. [15] [16] [17]Chemical structure of fasudil. AT-13148 [18]; BA-210; β-ElemeneBelumosudil; Chroman 1 [19] [20]; DJ4, which is a selective multi-specific ATP competitive inhibitor of activity of ROCK1 (IC50 of 5 nM), ROCK2 (IC50 of 50 nM), MRCKα (IC50 of 10 nM) and MRCKβ (IC50 of 100 nM) kinases without affecting activity of PAK1 and DMPK at 5 μM ...
RhoC expression has been associated with several signaling pathways and effectors. Here is a list of the ones found so far: IQGAP1 (IQ-domain GTP-ase Activating Protein): an effector of RhoC to enhance expression of cyclin E and cyclin D1. This resulted in cells being promoted to enter S phase more rapidly [16] ROCK-1 [12] [17]
Rac1 is a small (~21 kDa) signalling G protein (more specifically a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases.Members of this superfamily appear to regulate a diverse array of cellular events, including the control of GLUT4 [8] [9] translocation to glucose uptake, cell growth, cytoskeletal reorganization, antimicrobial cytotoxicity, [10] and the ...
The protein encoded by this gene is a serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions, and the activation of the c-fos serum response element. This protein, which is an isozyme of ROCK1 is a target for the small GTPase Rho.