title: Yeast adaptor protein, Nbp2p, is conserved regulator of fungal Ptc1p phosphatases and is involved in multiple signaling pathways.
abstract: Nbp2p is an Src homology 3 (SH3) domain-containing yeast protein that is involved in a variety of cellular processes. This small adaptor protein binds to a number of different proteins through its SH3 domain, and a region N-terminal to the SH3 domain binds to the protein phosphatase, Ptc1p. Despite its involvement in a large number of physical and genetic interactions, the only well characterized function of Nbp2p is to recruit Ptc1p to the high osmolarity glycerol pathway, which results in down-regulation of this pathway. In this study, we have discovered that Nbp2p orthologues exist in all Ascomycete and Basidiomycete fungal genomes and that all possess an SH3 domain and a conserved novel Ptc1p binding motif. The ubiquitous occurrence of these two features, which we have shown are both critical for Nbp2p function in Saccharomyces cerevisiae, implies that a conserved role of Nbp2p in all of these fungal species is the targeting of Ptc1p to proteins recognized by the SH3 domain. We also show that in a manner analogous to its role in the high osmolarity glycerol pathway, Nbp2p functions in the down-regulation of the cell wall integrity pathway through SH3 domain-mediated interaction with Bck1p, a component kinase of this pathway. Based on functional studies on the Schizosaccharomyces pombe and Neurospora crassa Nbp2p orthologues and the high conservation of the Nbp2p binding site in Bck1p orthologues, this function of Nbp2p appears to be conserved across Ascomycetes. Our results also clearly imply a function for the Nbp2p-Ptc1p complex other cellular processes.
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Stanger
authors.forename: Maryna
authors.initials: M
authors.lastname: Gorelik
authors.forename: Alan R
authors.initials: AR
authors.lastname: Davidson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002473:Cell Wall / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D009492:Neurospora crassa / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C487575:NBP2 protein, S cerevisiae; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2