CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration.

ArgBP2 is a multi-adapter protein involved in signal transduction associated to the cytoskeleton and was shown to regulate the migration and adhesion of pancreatic cancer cells thereby modulating their tumorigenicity. Here we describe the interaction of ArgBP2 with CIP4, a new associated protein identified by yeast two-hybrid. We found that both proteins modulated their reciprocal tyrosine phosphorylation catalyzed by the non-receptor tyrosine kinase c-Abl. We observed that, like ArgBP2, CIP4 directly interacted with WAVE1 and could enhance its phosphorylation by c-Abl. ArgBP2 and CIP4 acted synergistically to increase WAVE1 tyrosine phosphorylation. Finally, we could show that CIP4 was dispensable for the ArgBP2 induced blockade of cell migration whereas its overexpression was deleterious for this important function of ArgBP2. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.