Evidence for a CD4-associated calcium influx independent of the phosphoinositide transduction pathway in human T cells.
We recently showed, using human Jurkat T cell variants lacking the T cell receptor (TCR)/CD3 complex, that the lectin jacalin is able to trigger intracellular calcium increase provided that CD4 is expressed on the cell surface. Involvement of the CD4 molecule in jacalin-induced biological effects was furthermore demonstrated in differentiated U937 myelomonocytic cells expressing or not expressing CD4, and is confirmed here in human CD4-transfected mouse thymoma cells. In the present paper, we analyze the CD4-associated calcium response triggered by jacalin independently of the TCR/CD3 complex. We show that the observed calcium rise results from a direct long-lasting calcium influx from the outside without release of calcium from intracellular stores. We demonstrate that it is independent of the phosphoinositide phospholipase C transduction pathway. Moreover, we show that this peculiar calcium response can be blocked by protein tyrosine kinase inhibitors (herbimycin and genistein) giving evidence of the involvement of a protein tyrosine kinase, the best candidate of which is the CD4-associated p56lck. Altogether, our results suggest that, independently of the TCR/CD3 complex, CD4 may be involved in the triggering of a calcium signal dependent on a protein tyrosine kinase and independent of the phosphoinositide transduction pathway.
Lafont
V
V
Institut National de la Santé et de la Recherche Médicale (INSERM) U431, Université de Montpellier II, France.
Fischer
T
T
Zumbihl
R
R
Faure
S
S
Hivroz
C
C
Rouot
B
B
Favero
J
J
D000818:Animals; D016227:Benzoquinones; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000502:physiology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D047029:Lactams, Macrocyclic; D037102:Lectins / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D010716:Phosphatidylinositols / Q000502:physiology*; D051966:Phospholipase C gamma; D019000:Phosphotyrosine / Q000378:metabolism; D037121:Plant Lectins; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D016227:Benzoquinones; D015704:CD4 Antigens; D007295:Inositol Phosphates; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D037102:Lectins; D010716:Phosphatidylinositols; D037121:Plant Lectins; D011518:Proto-Oncogene Proteins; D011809:Quinones; C043696:jacalin; D017828:Rifabutin; D019000:Phosphotyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium