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PMID: 15256499 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast.

Genes & development ·Vol. 18 ·No. 14 ·2004-07-15 ·Pages 1695-708

Cullen PJ, Sabbagh W, Graham E, Irick MM, van Olden EK, Neal C, Delrow J, Bardwell L, Sprague GF

Abstract

Signaling molecules such as Cdc42 and mitogen-activated protein kinases (MAPKs) can function in multiple pathways in the same cell. Here, we propose one mechanism by which such factors may be directed to function in a particular pathway such that a specific response is elicited. Using genomic approaches, we identify a new component of the Cdc42- and MAPK-dependent signaling pathway that regulates filamentous growth (FG) in yeast. This factor, called Msb2, is a FG-pathway-specific factor that promotes differential activation of the MAPK for the FG pathway, Kss1. Msb2 is localized to polarized sites on the cell surface and interacts with Cdc42 and with the osmosensor for the high osmolarity glycerol response (HOG) pathway, Sho1. Msb2 is glycosylated and is a member of the mucin family, proteins that in mammalian cells promote disease resistance and contribute to metastasis in cancer cells. Remarkably, loss of the mucin domain of Msb2 causes hyperactivity of the FG pathway, demonstrating an inhibitory role for mucin domains in MAPK pathway activation. Taken together, our data suggest that Msb2 is a signaling mucin that interacts with general components, such as Cdc42 and Sho1, to promote their function in the FG pathway.

MeSH Terms
Amino Acid Sequence Blotting, Western Enzyme Activation GTPase-Activating Proteins/genetics,metabolism Intracellular Signaling Peptides and Proteins Membrane Proteins/metabolism Microscopy, Fluorescence Molecular Sequence Data Oligonucleotide Array Sequence Analysis Precipitin Tests Protein Structure, Tertiary Saccharomyces cerevisiae/growth & development,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Signal Transduction/physiology Two-Hybrid System Techniques cdc42 GTP-Binding Protein/metabolism
Chemicals
GTPase-Activating Proteins Intracellular Signaling Peptides and Proteins MSB2 protein, S cerevisiae Membrane Proteins SHO1 protein, S cerevisiae Saccharomyces cerevisiae Proteins cdc42 GTP-Binding Protein
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Cullen Paul J
Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229, USA.
Sabbagh Walid
Graham Ellie
Irick Molly M
van Olden Erin K
Neal Cassandra
Delrow Jeffrey
Bardwell Lee
Sprague George F
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1178604
Published
2004-07-15
Pages
1695-708
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC478191
Subset
IM
Grants
NIGMS NIH HHS · R01 GM030027 · United States
NIGMS NIH HHS · R01 GM060366 · United States
NIGMS NIH HHS · GM-30027 · United States
NIGMS NIH HHS · GM-60366 · United States
External Links
PubMed source DOI: 10.1101/gad.1178604 PMC Full Text View journal details
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