Regulation of CD43-induced U937 homotypic aggregation.
CD43 (leukosialin, sialophorin), a prominent component of the hemopoietic cell surface, has an enigmatic role in cell-cell interaction. The observation that CD43 ligation triggers homotypic aggregation of monoblastoid U937 cells has permitted analysis of this: CD43-induced aggregation was distinguishable from CD29- (also known as beta1 integrin) or CD98- (also known as 4F2, or fusion-related protein 1) induced aggregation, with different energy requirements and with partial dependence on beta2 integrins. Previous studies have focused on the role of CD43 ligation in tyrosine phosphorylation. However, in the homotypic adhesion assay, although there is initial tyrosine phosphorylation, protein tyrosine kinase inhibitors did not block aggregation. Therefore, other signaling pathways were examined. CD43 ligation induced protein tyrosine dephosphorylation, and protein tyrosine phosphatase inhibitors blocked aggregation. Activation of MAP kinases was not necessary. Cytoskeletal inhibitors amplified aggregation. Protein kinase C (PKC) inhibitors amplified aggregation, implicating PKC as a negative regulator. CD43 ligation up-regulated surface adhesion molecules and enhanced CD29- and CD98-induced aggregation. Thus, CD43 participation in cell-cell adhesion is under stringent control, involving both surface events and several different intracellular signaling pathways, acting together to regulate the process. These mechanisms add a further dimension to the potential role of CD43 in tissue immune responses.
D015703:Antigens, CD; D002449:Cell Aggregation / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027261:Fusion Regulatory Protein-1 / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D051917:Leukosialin; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D012795:Sialoglycoproteins / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D027261:Fusion Regulatory Protein-1; D019012:Integrin beta1; D051917:Leukosialin; D011956:Receptors, Cell Surface; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014443:Tyrosine; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases