INTERACTION OF 14-3-3 WITH SIGNALING PROTEINS IS MEDIATED BY THE RECOGNITION OF PHOSPHOSERINE

The highly conserved and ubiquitously expressed 14-3-3 family of prote ins bind to a variety of proteins involved in signal transduction and cell cycle regulation. The nature and specificity of 14-3-3 binding is , however, not known. Here we show that 14-3-3 is a specific phosphose rine-binding protein. Using a panel of phosphorylated peptides based o n Raf-1, we have defined the 14-3-3 binding motif and show that most o f the known 14-3-3 binding proteins contain the motif. Peptides contai ning the motif could disrupt 14-3-3 complexes and inhibit maturation o f Xenopus laevis oocytes. These results suggest that the interactions of 14-3-3 with signaling proteins are critical for the activation of s ignaling proteins. Our findings also suggest novel roles for serine/th reonine phosphorylation in the assembly of protein-protein complexes.