NISCH: Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension. Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons. Acts as a modulator of Rac-regulated signal transduction pathways. Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity. Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation. Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation. Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells. Inhibits lamellipodia formation, when overexpressed. Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures. 4 isoforms of the human protein are produced by alternative splicing.
Protein type: Receptor, GPCR; Motility/polarity/chemotaxis
Chromosomal Location of Human Ortholog: 3p21.1
Cellular Component: cytosol; early endosome; membrane; plasma membrane; recycling endosome
Molecular Function: identical protein binding; integrin binding; phosphoinositide binding; protein binding
Biological Process: actin cytoskeleton organization and biogenesis; apoptosis; glucose metabolic process; negative regulation of cell migration; norepinephrine secretion; Rac protein signal transduction; regulation of blood pressure; regulation of synaptic transmission, GABAergic
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