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 proteins 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 phosphoserine-binding protein. Using a panel of phosphorylated peptides based on Raf-1, we have defined the 14-3-3 binding motif and show that most of the known 14-3-3 binding proteins contain the motif. Peptides containing the motif could disrupt 14-3-3 complexes and inhibit maturation of Xenopus laevis oocytes. These results suggest that the interactions of 14-3-3 with signaling proteins are critical for the activation of signaling proteins. Our findings also suggest novel roles for serine/threonine phosphorylation in the assembly of protein-protein complexes.
Muslin
A J
AJ
Department of Medicine, Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Tanner
J W
JW
Allen
P M
PM
Shaw
A S
AS
D048948:14-3-3 Proteins; D016475:3T3 Cells / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D006825:Hybridomas; D007536:Isomerism; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase; D014981:Xenopus
D048948:14-3-3 Proteins; D004791:Enzyme Inhibitors; D010748:Phosphopeptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D010768:Phosphoserine; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf