PPP1R12A explained

Protein phosphatase 1 regulatory subunit 12A is an enzyme that in humans is encoded by the PPP1R12A gene.^{[1] [2]}

Myosin phosphatase target subunit 1, which is also called the myosin-binding subunit of myosin phosphatase, is one of the subunits of myosin phosphatase. Myosin phosphatase regulates the interaction of actin and myosin downstream of the guanosine triphosphatase Rho. The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle ^[3] and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP.RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP. RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase.^[2]

Interactions

PPP1R12A has been shown to interact with Interleukin 16.^[4]

Further reading

• Somlyo AP, Wu X, Walker LA, Somlyo AV . Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and phosphatases. . Rev. Physiol. Biochem. Pharmacol. . 134 . 201–34 . 1999 . 10087910 . 10.1007/3-540-64753-8_5. 978-3-540-64753-9 .
• Ziter FA, Wiser WC, Robinson A . Three-generation pedigree of a Möbius syndrome variant with chromosome translocation. . Arch. Neurol. . 34 . 7 . 437–42 . 1977 . 880069 . 10.1001/archneur.1977.00500190071011.
• Slee JJ, Smart RD, Viljoen DL . Deletion of chromosome 13 in Moebius syndrome. . J. Med. Genet. . 28 . 6 . 413–4 . 1991 . 1870098 . 10.1136/jmg.28.6.413 . 1016909 .
• Kimura K, Ito M, Amano M, etal . Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase) . Science . 273 . 5272 . 245–8 . 1996 . 8662509 . 10.1126/science.273.5272.245 . 1996Sci...273..245K . 37249779 .
• Ito M, Feng J, Tsujino S, etal . Interaction of smooth muscle myosin phosphatase with phospholipids. . Biochemistry . 36 . 24 . 7607–14 . 1997 . 9200713 . 10.1021/bi9702647 .
• Nakai K, Suzuki Y, Kihira H, etal . Regulation of myosin phosphatase through phosphorylation of the myosin-binding subunit in platelet activation. . Blood . 90 . 10 . 3936–42 . 1997 . 9354661 . 10.1182/blood.V90.10.3936. free .
• Somlyo AP . Kinases, myosin phosphatase and Rho proteins: curiouser and curiouser. . J. Physiol. . 516 . 3. 630 . 1999 . 10200412 . 10.1111/j.1469-7793.1999.0630u.x . 2269296 .
• Surks HK, Mochizuki N, Kasai Y, etal . Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. . Science . 286 . 5444 . 1583–7 . 1999 . 10567269 . 10.1126/science.286.5444.1583 .
• Feng J, Ito M, Ichikawa K, etal . Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. . J. Biol. Chem. . 274 . 52 . 37385–90 . 2000 . 10601309 . 10.1074/jbc.274.52.37385 . free .
• Arimura T, Suematsu N, Zhou YB, etal . Identification, characterization, and functional analysis of heart-specific myosin light chain phosphatase small subunit. . J. Biol. Chem. . 276 . 9 . 6073–82 . 2001 . 11067852 . 10.1074/jbc.M008566200 . free .
• Sebbagh M, Renvoizé C, Hamelin J, etal . Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. . Nat. Cell Biol. . 3 . 4 . 346–52 . 2001 . 11283607 . 10.1038/35070019 . 36187702 .
• Murányi A, Zhang R, Liu F, etal . Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity. . FEBS Lett. . 493 . 2–3 . 80–4 . 2001 . 11287000 . 10.1016/S0014-5793(01)02283-9 . 26428853 . free .
• Machida H, Ito M, Okamoto R, etal . Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene. . Biochim. Biophys. Acta . 1517 . 3 . 424–9 . 2001 . 11342221 . 10.1016/s0167-4781(00)00285-2.
• Kiss E, Murányi A, Csortos C, etal . Integrin-linked kinase phosphorylates the myosin phosphatase target subunit at the inhibitory site in platelet cytoskeleton. . Biochem. J. . 365 . Pt 1 . 79–87 . 2002 . 11931630 . 10.1042/BJ20011295 . 1222641 .
• Velasco G, Armstrong C, Morrice N, etal . Phosphorylation of the regulatory subunit of smooth muscle protein phosphatase 1M at Thr850 induces its dissociation from myosin. . FEBS Lett. . 527 . 1–3 . 101–4 . 2002 . 12220642 . 10.1016/S0014-5793(02)03175-7 . 39366441 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Kitazawa T, Eto M, Woodsome TP, Khalequzzaman M . Phosphorylation of the myosin phosphatase targeting subunit and CPI-17 during Ca2+ sensitization in rabbit smooth muscle. . J. Physiol. . 546 . Pt 3 . 879–89 . 2003 . 12563012 . 10.1113/jphysiol.2002.029306 . 2342583 .
• Seko T, Ito M, Kureishi Y, etal . Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle. . Circ. Res. . 92 . 4 . 411–8 . 2003 . 12600888 . 10.1161/01.RES.0000059987.90200.44 . free .

External links

• PPP1R12A Info with links in the Cell Migration Gateway

Notes and References

1. Takahashi N, Ito M, Tanaka J, Nakano T, Kaibuchi K, Odai H, Takemura K . Localization of the gene coding for myosin phosphatase, target subunit 1 (MYPT1) to human chromosome 12q15-q21 . Genomics . 44 . 1 . 150–2 . Nov 1997 . 9286714 . 10.1006/geno.1997.4859 .
2. Web site: Entrez Gene: PPP1R12A protein phosphatase 1, regulatory (inhibitor) subunit 12A.
3. News: Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855 but not Thr-697. Michael P. Walsh. etal. dead. https://web.archive.org/web/20110713204304/http://biosupport.licor.com/docs/2005/BJ20050237.pdf. 2011-07-13.
4. Bannert . Norbert . Vollhardt Karin . Asomuddinov Bakhtier . Haag Marion . König Herbert . Norley Stephen . Kurth Reinhard . Oct 2003 . PDZ Domain-mediated interaction of interleukin-16 precursor proteins with myosin phosphatase targeting subunits . J. Biol. Chem. . 278 . 43 . 42190–9 . United States. 0021-9258. 12923170 . 10.1074/jbc.M306669200 . free .