A role for autophosphorylation revealed by activated alleles of FUS3, the yeast MAP kinase homolog.
We have isolated dominant gain-of-function (gf) mutations in FUS3, a Saccharomyces cerevisiae mitogen-activated protein (MAP) kinase homolog, that constitutively activate the yeast mating signal transduction pathway and confer hypersensitivity to mating pheromone. Surprisingly, the phenotypes of dominant FUS3gf mutations require the two protein kinases, STE7 and STE11. FUS3gf kinases are hyperphosphorylated in yeast independently of STE7. Consistent with this, FUS3gf kinases expressed in Escherichia coli exhibit an increased ability to autophosphorylate on tyrosine in vivo. FUS3gf mutations suppress the signal transduction defect of a severely catalytically impaired allele of STE7. This finding suggests that the tyrosine-phosphorylated form of FUS3 is a better substrate for activation by STE7. Furthermore, these results imply that the degree of autophosphorylation of a MAP kinase determines its threshold of sensitivity to upstream signals.
Brill
J A
JA
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Elion
E A
EA
Fink
G R
GR
D000483:Alleles; D004789:Enzyme Activation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D005799:Genes, Dominant; D005800:Genes, Fungal; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C075580:FUS3 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases