Hemin-induced cap formation in lymphocytes: inhibition by protein tyrosine kinase inhibitors.
Hemin, an oxidant which is mitogenic for lymphocytes, was found to induce cap formation for Con A sites in murine and human lymphocytes and for IgG and Thy 1.2 sites in murine lymphocytes. Doses of hemin which induced capping also induced a redistribution of actin to a detergent-insoluble form. Similar to hemin, we found that heat shock also induced capping of Con A and IgG sites in murine splenocytes, as well as actin redistribution in human peripheral blood mononuclear cells. Specific inhibitors of protein tyrosine kinases, termed tyrphostins, were found to inhibit hemin-induced cap formation. In addition, ligand-dependent cap formation was also inhibited by tyrphostins. Hemin-induced cap formation may result from alteration in cytoskeletal structure and distribution. In addition, changes in membrane lipid composition induced by phospholipase C-gamma 1, known to be activated by protein tyrosine phosphorylation, may initiate actin polymerization and membrane-site redistribution.
Patya
M
M
Rogoff Institute, Beilinson Medical Center, Petah-Tikva, Israel.
Lander
H M
HM
Novogrodsky
A
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface; D002396:Catechols / Q000494:pharmacology; D003208:Concanavalin A; D006427:Hemin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007074:Immunoglobulin G; D007152:Immunologic Capping / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018800:Thy-1 Antigens; D020032:Tyrphostins
D000199:Actins; D000954:Antigens, Surface; D002396:Catechols; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009570:Nitriles; D018800:Thy-1 Antigens; D020032:Tyrphostins; D003208:Concanavalin A; C060152:tyrphostin 47; D006427:Hemin; D011505:Protein-Tyrosine Kinases