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PMID: 14685261 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nbp2 targets the Ptc1-type 2C Ser/Thr phosphatase to the HOG MAPK pathway.

The EMBO journal ·Vol. 23 ·No. 2 ·2004-01-28 ·Pages 302-11

Mapes J, Ota IM

Abstract

The yeast high osmolarity glycerol (HOG) pathway signals via the Pbs2 MEK and the Hog1 MAPK, whose activity requires phosphorylation of Thr and Tyr in the activation loop. The Ptc1-type 2C Ser/Thr phosphatase (PP2C) inactivates Hog1 by dephosphorylating phospho-Thr, while the Ptp2 and Ptp3 protein tyrosine phosphatases dephosphorylate phospho-Tyr. In this work, we show that the SH3 domain-containing protein Nbp2 negatively regulates Hog1 by recruiting Ptc1 to the Pbs2-Hog1 complex. Consistent with this role, NBP2 acted as a negative regulator similar to PTC1 in phenotypic assays. Biochemical analysis showed that Nbp2, like Ptc1, was required to inactivate Hog1 during adaptation. As predicted for an adapter, deletion of NBP2 disrupted Ptc1-Pbs2 complex formation. Furthermore, Nbp2 contained separate binding sites for Ptc1 and Pbs2: the novel N-terminal domain bound Ptc1, while the SH3 domain bound Pbs2. In addition, the Pbs2 scaffold bound the Nbp2 SH3 via a Pro-rich motif distinct from that which binds the SH3 domain of the positive regulator Sho1. Thus, Nbp2 recruits Ptc1 to Pbs2, a scaffold for both negative and positive regulators.

MeSH Terms
Adaptor Proteins, Signal Transducing Carrier Proteins/chemistry,physiology MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/metabolism Phosphoprotein Phosphatases/metabolism Protein Phosphatase 2 Protein Structure, Tertiary Saccharomyces cerevisiae/enzymology,metabolism Saccharomyces cerevisiae Proteins/chemistry,metabolism,physiology
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins NBP2 protein, S cerevisiae Saccharomyces cerevisiae Proteins HOG1 protein, S cerevisiae Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase Kinases PBS2 protein, S cerevisiae PTC1 protein, S cerevisiae Phosphoprotein Phosphatases Protein Phosphatase 2
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mapes James
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA.
Ota Irene M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600036
Published
2004-01-28
Epub
2003-00-18
Pages
302-11
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1271746
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600036 PMC Full Text View journal details
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