Introduction Recent years have witnessed the discovery of a growing number of short peptide segments that play critical biological roles. For instance, SH3 domains bind to sequences with a PxxP pattern, 14-3-3 domains to RxxSxP. Their short length (3-8 residues) and the fact that they often reside in nonglobular parts of proteins hinders their discovery both by traditional sequence comparison o...

The 14-3-3 proteins are a family of dimeric eukaryotic proteins that mediate both phosphorylation-dependent and -independent protein-protein interactions. Through these interactions, 14-3-3 proteins participate in the regulation of a wide range of cellular processes, including cell proliferation, cell cycle progression, and apoptosis. Because of their fundamental importance, 14-3-3 proteins hav...

In most higher eukaryotes, the predominantly phosphoprotein-binding 14-3-3 proteins are the products of a multigene family, with many organisms having 10 or more family members. However, current models for 14-3-3/phosphopeptide interactions suggest that there is little specificity among 14-3-3s for diverse phosphopeptide clients. Therefore, the existence of sequence diversity among 14-3-3s with...

UNLABELLED The parasite Cryptosporidium parvum has three 14-3-3 proteins: Cp14ε, Cp14a and Cp14b, with only Cp14ε similar to human 14-3-3 proteins in sequence, peptide-binding properties and structure. Structurally, Cp14a features the classical 14-3-3 dimer but with a uniquely wide pocket and a disoriented RRY triad potentially incapable of binding phosphopeptides. The Cp14b protein deviates fr...

REGULATION OF THE SUBCELLULAR LOCALIZATION OF THE G-PROTEIN SUBUNIT REGULATOR GPSM3 THROUGH DIRECT ASSOCIATION WITH 14-3-3 Patrick M. Giguère, Geneviève Laroche, Emily A. Oestreich, Joseph A. Duncan and David P. Siderovski* Department of Pharmacology and Division of Infectious Diseases, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599-7365; Department of P...

A family of proteins known as 14-3-3 is currently receiving increased attention by investigators studying a broad range of biological systems, including plants and invertebrates. The outstanding feature of this family is the extraordinarily high sequence conservation observed. Current thinking indicates that these proteins may function as regulators in signal transduction/phosphorylation mechan...

Institute for Translational Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455. Departments of Molecular and Human Genetics, Pediatrics, and Howard Hughes Medi...

In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in the structure. Functional studies revealed that compounds 1 and 2 potently inh...

Forward transport of proteins from the ER to the plasma membrane requires escape from the ER's retention machinery. Recent studies suggest that 14-3-3 proteins may mediate ER export of potassium channels destined for the plasma membrane by interfering with dibasic-motif-mediated retention.