Tyrosine kinase inhibition reduces the plateau phase of the calcium increase in response to progesterone in human sperm

Abstract

Progesterone (P) has previously been shown to induce a rapid increase in [Ca2+]i as well as tyrosine pbosphorylation of proteins in human spermatozoa. Both these effects are essential for induction of the acrosome reaction by P. We investigated a possible relationship between the P-induced calcium increase and tyrosine kinase activation, by evaluating the effect of the tyrosine kinase inhibitor genistein on these two effects. We found that preincubation with genistein abolished P-induced tyrosine phosphorylation of two sperm proteins of 97 and 75 kDa molecular weight and significantly inhibited the plateau phase of P-induced [CaZ÷]i increase without affecting the peak phase. Conversely, the plateau phase was enhanced by the tyrosine phosphatase inhibitor Na3VO 4. The effect of genistein was specific for P, since no inhibition was observed on the [Ca2+]i increase induced by thapsigargin, an inhibitor of endoplasmic Ca2+-ATPase previously shown to mobilize Ca 2+ in spermatozoa. These results indicate that tyrosine kinase activation is involved in the generation of the plateau phase of Ca 2+ influx induced by P, and suggest the possibility that two different pathways are involved in the induction of Ca 2+ entry by P in human sperm.

The effect of oviductal deleted in malignant brain tumor 1 over porcine sperm is mediated by a signal transduction pathway that involves pro-AKAP4 phosphorylation

“…Progesterone induces the tyrosine phosphorylation of 94 kDa (Tesarik et al 1993) and 97 kDa (Bonaccorsi et al 1995) human sperm proteins. Although similar in molecular weight, it is not known whether these proteins correspond to either human pro-AKAP82 or AKAP82 (actually pro-AKAP4 and AKAP4).…”

Nongenomic activation of spermatozoa by steroid hormones: Facts and fictions

“…A similar situation applies for the phospholipase C/inositol3phosphate/diacylglycerol/protein kinase (PLC/IP3/DAG/PKC) pathway: although the enhancing effect of P on inositol trisphophate (Thomas and Meizel, 1989) and diacylglycerol (O'Toole et al, 1996a) synthesis has been reported, blockers of phospholipase C do not appear to affect P-stimulated Ca 2+ fluxes (Harper et al, 2004), and whether the pathway is involved in the induction of AR remains controversial (O'Toole et al, 1996b;Bonaccorsi et al, 1998). P at micromolar concentrations has been also shown to promote tyrosine phosphorylation of sperm proteins (Tesarik et al, 1993;Luconi et al, 1995) and this pathway is involved in AR and Ca 2+ influx in response to the steroid (Martinez et al, 1999;Bonaccorsi et al, 1995). However, as for cAMP generation, tyrosine phosphorylation increase in response to P is small Kirkman-Brown et al, 2002) and its influence on Ca 2+ transients and AR is discussed (Kirkman-Brown et al, 2002).…”

Implication of Gβγ proteins and c-SRC tyrosine kinase in parathyroid hormone-induced signal transduction in rat enterocytes

“…In line with these observations, there is evidence demonstrating that PTH activates c-Src in osteoblastic cells through changes in tyrosine phosphorylation (Izbicka et al 1994 (Tsunoda et al 1996). Furthermore, Src family kinases have been implicated in the control of receptor-operated Ca 2+ influx in various cell types (Niklinska et al 1992, Lee et al 1993, Bonaccorsi et al 1995, Fleming et al 1995. Of interest, in colonic smooth muscle cells, the biphasic activation of ceramideinduced Src kinase activity was shown to be dependent on extracellular Ca 2+ in the second, sustained phase of activation (Ibitayo et al 1998).…”