BINDING OF CD44 TO HYALURONIC-ACID CAN BE INDUCED BY MULTIPLE SIGNALSAND REQUIRES THE CD44 CYTOPLASMIC DOMAIN

Human Jurkat T cells transfected with a human CD44H gene do not bind f luorescein-conjugated hyaluronic acid (F-HA). Activation of Jurkat CD4 4 transfectant is required for binding to F-HA. Binding can be induced by anti-CD3 monoclonal antibody (Mab), PMA, calcium ionophore, forsko lin, or a monoclonal anti-CD44 Mab (F10-44-2). Cytochalasin D, an inhi bitor of actin polymerization, inhibited both PMA-induced and anti-CD4 4 Mab-induced binding. In contrast, only PMA-induced binding was block ed by inhibitors of microtubule functions: colchicine or Taxol. Theref ore, binding induced by PMA and anti-CD44 Mab involves different cytos keletal proteins. The conclusion that interactions between CD44 and cy toskeletal proteins are important for binding was further supported by our observations that the cytoplasmic domain of CD44 is required for both PMA and anti-CD44 Mab-induced binding. Jurkat CD44 mutant transfe ctant lacking the last 23 amino acids of the cytoplasmic domain can be induced to bind FHA. In contrast, Jurkat mutant CD44 transfectant lac king the last 57 amino acids of the cytoplasmic domain was unable to b ind. Collectively, these data provide supportive evidence that binding activity of CD44 is under the regulation of multiple signal pathways and requires the presence of the cytoplasmic domain. (C) 1996 Academic Press, Inc.