3p0c

Structural highlights

Function

[NISCH_HUMAN] 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 (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). 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.^{[1] [2] [3] [4] [5]}

References

1. ↑ Piletz JE, Ivanov TR, Sharp JD, Ernsberger P, Chang CH, Pickard RT, Gold G, Roth B, Zhu H, Jones JC, Baldwin J, Reis DJ. Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization. DNA Cell Biol. 2000 Jun;19(6):319-29. PMID:10882231 doi:http://dx.doi.org/10.1089/10445490050043290
2. ↑ Dontenwill M, Pascal G, Piletz JE, Chen M, Baldwin J, Ronde P, Dupuy L, Urosevic D, Greney H, Takeda K, Bousquet P. IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells. Cell Death Differ. 2003 Aug;10(8):933-5. PMID:12868002 doi:http://dx.doi.org/10.1038/sj.cdd.4401275
3. ↑ Dontenwill M, Piletz JE, Chen M, Baldwin J, Pascal G, Ronde P, Dupuy L, Greney H, Takeda K, Bousquetd P. IRAS is an anti-apoptotic protein. Ann N Y Acad Sci. 2003 Dec;1009:400-12. PMID:15028619
4. ↑ Piletz JE, Deleersnijder W, Roth BL, Ernsberger P, Zhu H, Ziegler D. IRAS splice variants. Ann N Y Acad Sci. 2003 Dec;1009:419-26. PMID:15028621
5. ↑ Lim KP, Hong W. Human Nischarin/imidazoline receptor antisera-selected protein is targeted to the endosomes by a combined action of a PX domain and a coiled-coil region. J Biol Chem. 2004 Dec 24;279(52):54770-82. Epub 2004 Oct 8. PMID:15475348 doi:http://dx.doi.org/10.1074/jbc.M411315200