FIBRONECTIN MODULATES THE EFFECTS OF HIV-1 TAT ON THE GROWTH OF MURINE KAPOSIS SARCOMA-LIKE CELLS THROUGH THE DOWN-REGULATION OF TYROSINE PHOSPHORYLATION

HIV-1 Tat plays a role in the pathogenesis of Kaposi's sarcoma. We the refore investigated the effect of Tat on the growth of murine Kaposi's sarcoma-like spindle (TTB) cells derived from dermal lesions. We obse rved that Tat and a peptide corresponding to the carboxyl-terminal reg ion (Tat(65-80)) containing an RGD sequence inhibit TTB cell prolifera tion only when cells are cultured on fibronectin. This inhibitory effe ct correlates with redistribution of the alpha(v) integrin subunit on the surface of TTB cells and with down-regulation of tyrosine phosphor ylation of specific substrates due to an increased tyrosine phosphatas e activity. Indeed, phenylarsine oxide, a potent inhibitor of phosphot yrosine phosphatases, prevented the effects of Tat on TTB cells. We th erefore argue that the action of Tat on TTB cells is mediated by the R GD motif through an integrin-based cell signaling pathway involving th e activity of phosphotyrosine phosphatase(s), which would lead to a de crease in the levels of phosphotyrosine-containing proteins, among whi ch is erk-2/p42(MAPK).