Myosin-light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates the regulatory light chain of myosin II.[1] [edit] Isoforms Four different MLCK isoforms exist:[2] [edit] Function These enzymes are important in the mechanism of contraction in muscle. Once there is an influx of calcium cations (Ca++) into the muscle, either from the sarcoplasmic reticulum or, more importantly, from the extracellular space, contraction of smooth muscle fibers may begin. First, the calcium will bind to calmodulin. This binding will activate MLCK, which will go on to phosphorylate the myosin light chain at serine residue 19. This will enable the myosin crossbridge to bind to the actin filament and allow contraction to begin (through the crossbridge cycle). Since smooth muscle does not contain a troponin complex like striated muscle does, this mechanism is the main pathway for regulating smooth muscle contraction. [edit] See also [edit] References - ^ Gao Y, Ye LH, Kishi H, Okagaki T, Samizo K, Nakamura A, Kohama K (June 2001). "Myosin light chain kinase as a multifunctional regulatory protein of smooth muscle contraction". IUBMB Life 51 (6): 337–44. PMID 11758800.
- ^ Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome". Science (journal) 298 (5600): 1912–34. doi:10.1126/science.1075762. PMID 12471243.
[edit] Further reading - Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.
- Clayburgh DR, Rosen S, Witkowski ED, et al. (2005). "A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability.". J. Biol. Chem. 279 (53): 55506–13. doi:10.1074/jbc.M408822200. PMID 15507455.
- Wang F, Graham WV, Wang Y, et al. (2005). "Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression.". Am. J. Pathol. 166 (2): 409–19. PMID 15681825.
- Russo JM, Florian P, Shen L, et al. (2005). "Distinct temporal-spatial roles for rho kinase and myosin light chain kinase in epithelial purse-string wound closure.". Gastroenterology 128 (4): 987–1001. PMID 15825080.
- Shimizu S, Yoshida T, Wakamori M, et al. (2006). "Ca2+-calmodulin-dependent myosin light chain kinase is essential for activation of TRPC5 channels expressed in HEK293 cells.". J. Physiol. (Lond.) 570 (Pt 2): 219–35. doi:10.1113/jphysiol.2005.097998. PMID 16284075.
- Kim MT, Kim BJ, Lee JH, et al. (2006). "Involvement of calmodulin and myosin light chain kinase in activation of mTRPC5 expressed in HEK cells.". Am. J. Physiol., Cell Physiol. 290 (4): C1031–40. doi:10.1152/ajpcell.00602.2004. PMID 16306123.
- Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMID 16344560.
- Connell LE, Helfman DM (2007). "Myosin light chain kinase plays a role in the regulation of epithelial cell survival.". J. Cell. Sci. 119 (Pt 11): 2269–81. doi:10.1242/jcs.02926. PMID 16723733.
- Seguchi O, Takashima S, Yamazaki S, et al. (2007). "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart.". J. Clin. Invest. 117 (10): 2812–24. doi:10.1172/JCI30804. PMID 17885681.
[edit] External links This article incorporates text from the United States National Library of Medicine, which is in the public domain.
| Kinases: Serine/threonine-specific protein kinases | | | Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20) | | | | LATS1, LATS2, MAST1, MAST2, STK38, STK38L, CIT, ROCK1, SGK, SGK2, SGK3, Protein kinase B ( AKT1, AKT2, AKT3), Ataxia telangiectasia mutated, Mammalian target of rapamycin, EIF-2 kinases ( PKR, HRI), Wee1 ( WEE1) | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - | | | | | | | | | | | | | | | | Protein kinase C, Protein kinase Cζ, PKC alpha, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, PRKCQ, Protein kinase N1, PKN2, PKN3, | | | | | | | | | | | | | | | | BRSK2, CAMK1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, MLCK, CASK, CHEK1, CHEK2, DAPK1, DAPK2, DAPK3, STK11, MAPKAPK2, MAPKAPK3, MAPKAPK5, MARK1, MARK2, MARK3, MARK4, MELK, MKNK1, MKNK2, NUAK1, NUAK2, OBSCN, PASK, PHKG1, PHKG2, PIM1, PIM2, PKD1, PRKD2, PRKD3, PSKH1, SNF1LK2, KIAA0999, STK40, SNF1LK, SNRK, SPEG, TSSK2, Kalirin, TRIB1, TRIB2, TRIB3, TRIO, Titin, DCLK1 | | | Myosin light-chain kinase (EC 2.7.11.18) | | | | | | | | | | | | | | Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30) | | | | | | | | CDK1, CDK2, CDKL2, CDK3, CDK4, CDK5, CDKL5, CDK6, CDK7, CDK8, CDK9, CDK10, CDC2L5, CRKRS, PCTK1, PCTK2, PCTK3, PFTK1, CDC2L1 | | | | | | | | Extracellular signal-regulated ( MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK12, MAPK15), C-Jun N-terminal ( MAPK8, MAPK9, MAPK10), P38 mitogen-activated protein ( MAPK11, MAPK13, MAPK14) | | | | MAP kinase kinase kinases ( MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8) RAFs ( ARAF, BRAF, KSR1, KSR2) MLKs ( MAP3K12, MAP3K13, MAP3K9, MAP3K10, MAP3K11, MAP3K7, ZAK) CDC7 | | | | | | | | - | | | | - | | | | - | | | | Bone morphogenetic protein receptors ( BMPR1, BMPR1A, BMPR1B, BMPR2), ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, Anti-Müllerian hormone receptor | | | | | | | |