Contortrostatin activates ERK2 and tyrosine phosphorylation events via distinct pathways.
We report that cells adhering to contortrostatin show transient increases in activation of Extracellular signal Regulated Kinase 2 (ERK2). The kinetics and degree of activation are similar to cells adhering to fibronectin or vitronectin. We have recently shown that contortrostatin induces tyrosine phosphorylation in tumor cells. Contortrostatin is shown here to stimulate activation of ERK2 in suspended cells, but this activation follows a different dose-response pattern than contortrostatin-induced tyrosine phosphorylation. Since contortrostatin induces tyrosine phosphorylation via alphavbeta3, we explored the effects of an alphavbeta3-blocking antibody, 7E3, on contortrostatin-stimulated ERK2 activation. While 7E3 completely blocks the effect of contortrostatin on tyrosine phosphorylation, this antibody had no effect on activation of ERK2. In cells lacking expression of alphavbeta3, tyrosine phosphorylation was unaffected by contortrostatin treatment, but ERK2 was activated. This is strong evidence that contortrostatin is regulating tyrosine phosphorylation events and ERK2 activation via separate pathways and through different integrin receptors.
Ritter
M R
MR
Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA.
Markland
F S
FS
D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D019483:Disintegrins / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism
D019483:Disintegrins; D005353:Fibronectins; D016023:Integrins; D019096:Vitronectin; C403494:contortrostatin; D014443:Tyrosine; D019950:Mitogen-Activated Protein Kinase 1