LMTK2 explained

Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 (LMTK2) is an enzyme that in humans is encoded by the LMTK2 gene.^{[1] [2]}

Function

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 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]

Interactions

LMTK2 has been shown to interact with PPP1CA,^[4] Cyclin-dependent kinase 5^[5] and PPP1R2.^[4]

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 . Multiple newly identified loci associated with prostate cancer susceptibility . Nature Genetics . 40 . 3 . 316–21 . Mar 2008 . 18264097 . 10.1038/ng.90 . 30968525 .
• Chibalina MV, Seaman MN, Miller CC, Kendrick-Jones J, Buss F . Myosin VI and its interacting protein LMTK2 regulate tubule formation and transport to the endocytic recycling compartment . Journal of Cell Science . 120 . Pt 24 . 4278–88 . Dec 2007 . 18029400 . 2621362 . 10.1242/jcs.014217 .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . Nov 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Wang H, Brautigan DL . 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 . Nov 2006 . 16887929 . 10.1074/mcp.M600188-MCP200 . free .
• Kesavapany S, Lau KF, Ackerley S, Banner SJ, Shemilt SJ, Cooper JD, Leigh PN, Shaw CE, McLoughlin DM, Miller CC . Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase . The Journal of Neuroscience . 23 . 12 . 4975–83 . Jun 2003 . 12832520 . 10.1523/JNEUROSCI.23-12-04975.2003. 6741199 . free .
• Wang H, Brautigan DL . A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2 . The Journal of Biological Chemistry . 277 . 51 . 49605–12 . Dec 2002 . 12393858 . 10.1074/jbc.M209335200 . free .
• Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . 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 . Jun 1999 . 10470851 . 10.1093/dnares/6.3.197 . free .

Notes and References

1. Kawa S, Fujimoto J, Tezuka T, Nakazawa T, Yamamoto T . Involvement of BREK, a serine/threonine kinase enriched in brain, in NGF signalling . Genes to Cells . 9 . 3 . 219–32 . Mar 2004 . 15005709 . 10.1111/j.1356-9597.2004.00714.x . 26059849 . free .
2. Web site: Entrez Gene: LMTK2 lemur tyrosine kinase 2.
3. Shah K, Bradbury NA . Lemur Tyrosine Kinase 2, a novel target in prostate cancer therapy . Oncotarget . 6 . 16 . 14233–46 . Jun 2015 . 26008968 . 10.18632/oncotarget.3899 . 4546463.
4. Wang H, Brautigan DL . A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2 . The Journal of Biological Chemistry . 277 . 51 . 49605–12 . Dec 2002 . 12393858 . 10.1074/jbc.M209335200 . free .
5. Kesavapany S, Lau KF, Ackerley S, Banner SJ, Shemilt SJ, Cooper JD, Leigh PN, Shaw CE, McLoughlin DM, Miller CC . Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase . The Journal of Neuroscience . 23 . 12 . 4975–83 . Jun 2003 . 12832520 . 6741199 . 10.1523/JNEUROSCI.23-12-04975.2003 .