Structural highlights
Function
[RON_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.[1] [2] [3]
Publication Abstract from PubMed
A complex of RON(M1254T) with AMP-PNP and Mg(2+) reveals a substratelike positioning of Tyr1238 as well as likely catalysis-competent placement of the AMP-PNP and Mg(2+) components and indicates a tendency for cis phosphorylation. The structure shows how the oncogenic mutation may cause the constitutive activation and suggests a mechanistic hypothesis for the autophosphorylation of receptor tyrosine kinases.
The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis.,Wang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, Mulvihill MJ, Crew AP Biochemistry. 2010 Sep 21;49(37):7972-4. PMID:20726546[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, Breathnach R. Identification of the ron gene product as the receptor for the human macrophage stimulating protein. Science. 1994 Oct 7;266(5182):117-9. PMID:7939629
- ↑ Nanney LB, Skeel A, Luan J, Polis S, Richmond A, Wang MH, Leonard EJ. Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury. J Invest Dermatol. 1998 Oct;111(4):573-81. PMID:9764835 doi:http://dx.doi.org/10.1046/j.1523-1747.1998.00332.x
- ↑ Feres KJ, Ischenko I, Hayman MJ. The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells. Oncogene. 2009 Jan 15;28(2):279-88. doi: 10.1038/onc.2008.383. Epub 2008 Oct 6. PMID:18836480 doi:http://dx.doi.org/10.1038/onc.2008.383
- ↑ Wang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, Mulvihill MJ, Crew AP. The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis. Biochemistry. 2010 Sep 21;49(37):7972-4. PMID:20726546 doi:10.1021/bi100409w
