Different signal transduction pathways are involved during human sperm capacitation induced by biological and pharmacological agents.
Human sperm capacitation involves complex signal transduction mechanisms during which double phosphorylation of the threonine-glutamine-tyrosine motif (P-Thr-Glu-Tyr-P) occurs in some sperm proteins. The objective of this study was to investigate the regulation of this process. Fetal cord serum ultrafiltrate (FCSu), follicular fluid ultrafiltrate (FFu), progesterone and a combination of N(6),2'-O-dibutyryl cAMP (dbcAMP; cell permeant analogue of cAMP) and 3-isobutyl-1-methylxanthine (IBMX; phosphodiesterase inhibitor) were used as inducers of capacitation alone or in combination with inhibitors of protein kinase A (H89), protein kinase C (chelerythrine), protein tyrosine kinase (tyrphostin A47, PP2) and of dual specificity kinase (MEK-like kinases; PD98059). The level of P-Thr-Glu-Tyr-P in sperm proteins of 80 and 105 kDa during capacitation induced by FCSu, FFu and progesterone was regulated by a similar signal transduction pathway and involved receptor type protein tyrosine kinase and dual specificity kinase (MEK or MEK-like) but not protein kinase A or C. However, the level of P-Thr-Glu-Tyr-P in these sperm proteins during capacitation induced by dbcAMP+IBMX was mainly mediated through protein kinase A and C and receptor type protein tyrosine kinase, but not by dual specificity kinase. In conclusion, human sperm capacitation induced by some biological and pharmacological agents is regulated through very different signal transduction pathways.
Urology Research Laboratory, H6.44, Royal Victoria Hospital and McGill University, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada. jthundathil@hotmail.com
J
J
Thundathil
E
E
de Lamirande
C
C
Gagnon
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000470:Alkaloids; D020816:Amino Acid Motifs; D053119:Benzophenanthridines; D003994:Bucladesine / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood; D005419:Flavonoids / Q000494:pharmacology; D015571:Follicular Fluid; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D048728:MAP Kinase Kinase Kinase 1; D008297:Male; D010617:Phenanthridines / Q000494:pharmacology; D010766:Phosphorylation; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013075:Sperm Capacitation / Q000187:drug effects* / Q000502:physiology*; D013449:Sulfonamides; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007546:Isoquinolines; D010617:Phenanthridines; D029589:Seminal Plasma Proteins; D013449:Sulfonamides; D020032:Tyrphostins; C060152:tyrphostin 47; D014443:Tyrosine; D011374:Progesterone; D003994:Bucladesine; C016299:chelerythrine; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D015056:1-Methyl-3-isobutylxanthine