Nuclear shuttling of yeast scaffold Ste5 is required for its recruitment to the plasma membrane and activation of the mating MAPK cascade.
Localization of Ste5 to GP at the plasma membrane is essential for transmission of the pheromone signal to associated MAP kinase cascade enzymes. Here, we show that this crucial localization requires prior shuttling of Ste5 through the nucleus. Ste5 shuttles through the nucleus constitutively during vegetative growth. Pheromone enhances nuclear export of Ste5, and this pool translocates vectorially to the cell periphery. Remarkably, Ste5 that cannot transit the nucleus is unable to localize at the periphery and activate the pathway, while Ste5 with enhanced transit through the nucleus has enhanced ability to localize to the periphery and activate the pathway. This novel regulatory scheme may ensure that cytoplasmic Ste5 does not activate downstream kinases in the absence of pheromone and could be applicable to other membrane-recruited signaling proteins.
Mahanty
S K
SK
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wang
Y
Y
Farley
F W
FW
Elion
E A
EA
D048868:Adaptor Proteins, Signal Transducing; D001692:Biological Transport; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D000072235:Mating Factor; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000502:physiology*; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D010455:Peptides; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000072235:Mating Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins