Beta 2-integrin-mediated signal up-regulates counterreceptor ICAM-1 expression on human monocytic cell line THP-1 through tyrosine phosphorylation
Abstract
Intracellular cross-talk between LFA-1 and its counter receptor, intercellular adhesion molecule-1 (ICAM-1), on human monocytic cell line THP-1 was analyzed. Stimulation with mAb YH384 specific for LFA-1 alpha (CD11a) up-regulated ICAM-1 expression on THP-1 cells. Cell surface expression of ICAM-1 on THP-1 cells was dose-dependently up-regulated and reached the maximal level 24 hr after stimulation with mAb YH384. Up-regulation of ICAM-1 by mAb YH384 was further confirmed by Northern blotting analysis at the mRNA level, and the maximal message of ICAM-1 was observed 4 hr after stimulation. mAb YH384-induced upregulation of cell surface expression was ICAM-1-specific, and the expression of the other nine molecules tested was not augmented. Up-regulation of ICAM-1 was also observed following stimulation with other mAb specific for CD11a (S6F1), CD11b (JML-H11), and CD18 (IB4); all of these mAb recognized members of the beta 2-integrin family, but not with isotype-matched control mAb. The mAb 4B4 (specific for beta 1-integrin) similarly, but more weakly, augmented ICAM-1 expression. The effect of mAb YH384 on expression of ICAM-1 was dose-dependently suppressed by treatment with herbimycin A or genistein, both inhibitors of tyrosi...Continue Reading
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Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase
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