Contortrostatin activates ERK2 and tyrosine phosphorylation events via distinct pathways

We report that cells adhering to contortrostatin show transient increases i n activation of Extracellular signal Regulated Kinase 2 (ERK2). The kinetic s and degree of activation are similar to cells adhering to fibronectin or vitronectin. We have recently shown that contortrostatin induces tyrosine p hosphorylation in tumor cells. Contortrostatin is shown here to stimulate a ctivation of ERK2 in suspended cells, but this activation follows a differe nt dose-response pattern than contortrostatin-induced tyrosine phosphorylat ion. Since contortrostatin induces tyrosine phosphorylation via alpha v bet a 3, we explored the effects of an alpha v beta 3-blocking antibody, 7E3, o n contortrostatin-stimulated ERK2 activation. While 7E3 completely blocks t he effect of contortrostatin on tyrosine phosphorylation, this antibody had no effect on activation of ERK2. In cells lacking expression of alpha v be ta 3, tyrosine phosphorylation was unaffected by contortrostatin treatment, but ERK2 was activated. This is strong evidence that contortrostatin is re gulating tyrosine phosphorylation events and ERK2 activation via separate p athways and through different integrin receptors. (C) 2000 Academic Press.