Killing two birds with one RKIP

Analysis of metastatic prostate cancers has identified the Raf kinase inhibitory protein (RKIP) as a suppressor of metastases. Previous studies demonstrated that RKIP binds to Raf-1 and prevents the activation of the extracellular regulated kinase (ERK) cascade. New work shows that phosphorylation of RKIP by protein kinase C disassociates RKIP from Raf-1 and stimulates its binding to, and inhibition of G-protein-coupled receptor kinase 2 (GRK2). This switching enhances signaling by activation of the ERK pathway and by decreased receptor desensitization.