The LMTK2 enzyme belongs to both the protein kinase and the tyrosine kinase families. It contains N-terminus transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity. This protein interacts with several other proteins, such as androgen receptor, inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosphorylates other proteins, and is itself also phosphorylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein is involved in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis.[2]
Clinical significance
Loss of LMTK2 has been implicated to play a role in development of prostate cancer.[3]
↑ 4.04.1Wang H, Brautigan DL (Dec 2002). "A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2". The Journal of Biological Chemistry. 277 (51): 49605–12. doi:10.1074/jbc.M209335200. PMID12393858.
↑Kesavapany S, Lau KF, Ackerley S, Banner SJ, Shemilt SJ, Cooper JD, Leigh PN, Shaw CE, McLoughlin DM, Miller CC (Jun 2003). "Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): 4975–83. PMID12832520.
Further reading
Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J, Field HI, Southey MC, Severi G, Donovan JL, Hamdy FC, Dearnaley DP, Muir KR, Smith C, Bagnato M, Ardern-Jones AT, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Cox A, Lewis S, Brown PM, Jhavar SG, Tymrakiewicz M, Lophatananon A, Bryant SL, Horwich A, Huddart RA, Khoo VS, Parker CC, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Fisher C, Jamieson C, Cooper CS, English DR, Hopper JL, Neal DE, Easton DF (Mar 2008). "Multiple newly identified loci associated with prostate cancer susceptibility". Nature Genetics. 40 (3): 316–21. doi:10.1038/ng.90. PMID18264097.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
Wang H, Brautigan DL (Nov 2006). "Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase". Molecular & Cellular Proteomics. 5 (11): 2124–30. doi:10.1074/mcp.M600188-MCP200. PMID16887929.
Kesavapany S, Lau KF, Ackerley S, Banner SJ, Shemilt SJ, Cooper JD, Leigh PN, Shaw CE, McLoughlin DM, Miller CC (Jun 2003). "Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): 4975–83. PMID12832520.
Wang H, Brautigan DL (Dec 2002). "A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2". The Journal of Biological Chemistry. 277 (51): 49605–12. doi:10.1074/jbc.M209335200. PMID12393858.
Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jun 1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID10470851.