To the HCO- -dependent activation of three PKA by sAC/cAMP and

Towards the HCO- -dependent activation of 3 PKA by sAC/cAMP and the other entails the down-regulation of Ser/Thr phosphatases (i.e. PP1g2 and/or PP2A) by SFK. The crossroads in between both signaling pathways is located at the PKA-Ser/Thr phosphorylation step. In spite with the early onset (1 min) of cAMP and PKA-dependent phosphorylation, human sperm need no less than 6 h incubation under capacitating circumstances to reach a functional capacitation state (i.e. AR and sperm fertilizing capability).Signaling pathways involved in human sperm capacitationChang MC. Fertilizing capacity of spermatozoa deposited into fallopian tubes. Nature 1951;168:697 698. Chen Y, Cann MJ, Litvin TN, Iourgenko V, Sinclair ML, Levin LR, Buck J. Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 2000;289:625628. Cohen DJ, Ellerman DA, Busso D, Morgenfeld M, Piazza A, Hayashi M, Young ET, Kasahara M, Cuasnicu PS. Evidence that human epididymal protein ARP plays a role in gamete fusion by means of complementary web sites on the surface from the human oocyte. Biol Reprod 2001;65:10001005. Copsel S, Garcia C, Diez F, Vermeulem M, Baldi A, Bianciotti LG, Russel FG, Shayo C, Davio C. Multidrug resistance protein four (MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cell proliferation and differentiation. J Biol Chem 2011;286:69796988. Da Ros VG, Munuce MJ, Cohen DJ, Marin-Briggiler CI, Busso D, Visconti PE, Cuasnicu PS. Bicarbonate is required for migration of sperm epididymal protein DE (CRISP-1) towards the equatorial segment and expression of rat sperm fusion potential. Biol Reprod 2004;70:13251332. Esposito G, Jaiswal BS, Xie F, Krajnc-Franken MA, Robben TJ, Strik AM, Kuil C, Philipsen RL, Van Duin M, Conti M et al. Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc Natl Acad Sci USA 2004;101:2993 2998. Fardilha M, Esteves SL, Korrodi-Gregorio L, Pelech S, da Cruz E Silva OA, da Cruz e Silva E. Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility. Mol Hum Reprod 2011a; 17:466477. Fardilha M, Esteves SL, Korrodi-Gregorio L, Vintem AP, Domingues SC, Rebelo S, Morrice N, Cohen PT, da Cruz E Silva OA, da Cruz e Silva EF.D(+)-Galactosamine (hydrochloride) Identification of your human testis protein phosphatase 1 interactome.DAMGO Biochem Pharmacol 2011b;82:1403 1415.PMID:24278086 Ficarro S, Chertihin O, Westbrook VA, White F, Jayes F, Kalab P, Marto JA, Shabanowitz J, Herr JC, Hunt DF et al. Phosphoproteome evaluation of capacitated human sperm. Proof of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 for the duration of capacitation. J Biol Chem 2003;278:1157911589. Galantino-Homer HL, Visconti PE, Kopf GS. Regulation of protein tyrosine phosphorylation through bovine sperm capacitation by a cyclic adenosine 3 5 -monophosphate-dependent pathway. Biol Reprod 1997; 56:707719. Hess KC, Jones BH, Marquez B, Chen Y, Ord TS, Kamenetsky M, Miyamoto C, Zippin JH, Kopf GS, Suarez SS et al. The `soluble’ adenylyl cyclase in sperm mediates various signaling events needed for fertilization. Dev Cell 2005;9:249 259. Hu X, Wu X, Xu J, Zhou J, Han X, Guo J. Src kinase up-regulates the ERK cascade by way of inactivation of protein phosphatase 2A following cerebral ischemia. BMC Neurosci 2009;ten:74. Ishihara H, Martin BL, Brautigan DL, Karaki H, Ozaki H, Kato Y, Fusetani N, Watabe S, Hashimoto K, Uemura D et al. Calyculin A and okadaic acid:inhibitors of protein phosphatase acti.