title: Identification of motility-associated progesterone-responsive differentially phosphorylated proteins.
abstract: Progesterone is one of the regulators of sperm motility and hyperactivation. In human spermatozoa, the effects of progesterone are thought to be mediated by protein phosphorylation. In the present study, we identified 22 proteins that are differentially phosphorylated (12 phosphorylated and 10 dephosphorylated) by progesterone in human spermatozoa. Functionally, the differentially phosphorylated proteins are predicted to have cytoskeletal localisation and to be associated with sperm motility. 5µM of progesterone to capacitated increased the phosphorylation of tyrosine residues in the principal piece and protein tyrosine kinase activity increased by almost 3.5-fold. For the first time, we demonstrate that tyrosine phosphatases are also activated in response to progesterone and that inhibition of tyrosine phosphatases attenuates dephosphorylation of flagellar proteins. We propose that progesterone activates both kinase and phosphatase pathways, leading to changes in the phosphorylation of many proteins in sperm flagella to increase motility.
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health, Indian Council of Medical Research, JM Street, Parel, Mumbai 400012, India.
authors.forename: V
authors.initials: V
authors.lastname: Sagare-Patil
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health, Indian Council of Medical Research, JM Street, Parel, Mumbai 400012, India.
authors.forename: D
authors.initials: D
authors.lastname: Modi
mesh_terms: D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005407:Flagella / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D018715:Microscopy, Video; D008954:Models, Biological; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D055101:Semen Analysis; D013075:Sperm Capacitation / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D014443:Tyrosine; D011374:Progesterone; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases