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Amino and carboxyl termini are unique positions in a polypeptide. They tend to be exposed in folded three dimensional structures. Diversity and functional significance of C-terminal sequences have been appreciated from studies of PDZ and PEX domains. Signaling 14-3-3 protein signaling by recognizing phosphorylated peptides plays a critical role in a variety(More)
The generic membrane trafficking signals of internal RXR and carboxyl-terminal KKXX motifs direct intracellular endoplasmic reticulum (ER) localization of the signal-bearing proteins. These signaling motifs play a critical role in partitioning proteins into designated subcellular compartments by functioning as an intracellular "zip code." In the process of(More)
The pore-forming subunit of the large-conductance Ca(2+)-dependent K(+) (Slo1) channel is encoded by one gene. However, the functional properties of Slo1 channels are diverse in part because of their numerous regulatory mechanisms including posttranslational modification and alternative splicing. In particular, multiple splice variants of the pore-forming(More)
The density and composition of cell surface proteins are major determinants for cellular functions. Regulation of cell surface molecules occurs at several levels, including the efficiency of surface transport, and is therefore of great interest. As the major phosphoprotein-binding modules, 14-3-3 proteins are known for their crucial roles in a wide range of(More)
Membrane trafficking is dictated by dynamic molecular interactions involving discrete determinants in the cargo proteins and the intracellular transport machineries. We have previously reported that cell surface expression of GPR15, a G protein-coupled receptor (GPCR) that serves as a co-receptor for HIV, is correlated with the mode III binding of 14-3-3(More)
Diverse functions of 14-3-3 proteins are directly coupled to their ability to interact with targeted peptide substrates. RSX(pS/pT)XP and RXPhiX(pS/pT)XP are two canonical consensus binding motifs for 14-3-3 proteins representing the two common binding modes, modes I and II, between 14-3-3 and internal peptides. Using a genetic selection, we have screened a(More)
The carboxylated (C)-terminus of proteins, which includes the single terminal alpha-carboxyl group and preceding residues, is uniquely positioned to serve as a recognition signature for a variety of cell-biological processes, including protein targeting, subcellular anchoring and the static and dynamic formation of macromolecular complexes. The terminal(More)
Excitotoxicity is the major cause of many neurologic disorders including stroke. Potassium currents modulate neuronal excitability and therefore influence the pathological process. A-type potassium current (I(A)) is one of the major voltage-dependent potassium currents, yet its roles in excitotoxic cell death are not well understood. We report that,(More)
The regulation of protein expression on the cell surface membrane is an important component of the cellular response to extracellular signalling. The translation of extracellular signalling into specific protein localization often involves the post-translational modification of cargo proteins. Using a genetic screen of random peptides, we have previously(More)