cullen lecture 6: signal transduction in fungi. filamentous growth saccharomyces cerevisiae (g....
TRANSCRIPT
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Cullen Lecture 6:Signal Transduction in
Fungi
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Filamentous GrowthFilamentous Growth
Saccharomyces cerevisiae (G . Fink)And fungal pathogens
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Specificity of Signaling Pathways Containing
Cdc42and MAPK Components
in Yeast
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Signal Transduction Pathways Control Fungal Behavior
Stimulus Response New Cell TypeSignaling
Cell
Nucleus
Receptor
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FGP
?
Cdc42/Ste20
Ste11Ste7Kss1
Ste12/Tec1
Filamentous Growth Pathway
Receptor:
GTPase/PAK:
MAPK3:MAPK2:MAPK:
Txn1/Txn2:
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Yeast Signaling Proteins are Homologous to Mammalian
Counterparts
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http://www.hhmi.org/research/investigators/wu.html
“Cross-Talk” in Signaling Pathways
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Prediction of Specificity Factors
Sho1Ste2042
??
Cell Wall
Membrane
FGP
Sho1 + ?
Cdc42/Ste20
Ste11Ste7Kss1
Ste12/Tec1
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Characterize the Msb2 Protein
Msb2 is glycosylated
Msb2 is an Integral Membrane Protein
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Msb2
Topology of Msb2
Cell Wall
Plasma Membrane
Glycosylated
Integral Membrane
Cell Surface
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Ste2042
Msb2
Sho1
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Topology and Domain Structure of Msb2
Mucin-HomologyDomain
SignalSequence
Membrane-SpanningDomain
100 AA
Extracellular Cytoplasmic
Glycosylation Sites
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Msb2
Msb2 is a Mucin
Cell Wall
Plasma Membrane
Mucin-HomologyDomain
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Mucins are Gross but Important
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Mucins in Mammalian Cells
Disease resistance
Metastasis
Signaling role
MUC1 and MUC4
Docks ß-cateninGrb2-Sos-Ras-MEK-ERK2 pathway
Erb2/Her2/NeuErb2-Erb3
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Msb2’s Mucin-Homology Domain
100 AA
N…(698)S Q V S D T SV S Y T T S S S S V S Q V S D T PV S Y T T S S S S V S Q V S D T PV S Y T T S S S S V S Q V S D T PV S Y T T S S S S V S Q V S D T PV S Y T T S S S S V S Q V S D T SV P S T S S S S S V S Q V S D T PV P S T S S S S S V S Q (818) …C
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wt mucin
Msb2 w/o the Mucin Domain is Hyperactive
Is the Mucin Domain Required for FG Pathway Activity?
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Mucin Repeats Are Inhibitory
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Repeats are Homologous at the Nucleotide Level
Undergo Recombination-Mediated Deletion
Analysis of the Mucin Repeats (Continued)
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Msb2-Dependence of MAPK Specificity
PRP
Receptor
Fus3
FGP
Msb2
Kss1
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Msb2 induces Kss1~P but not Fus3~P
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Msb2 induces Kss1~P but not Fus3~P
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Conclusions
Msb2 is a glycosylated integral-membrane cell-surface signaling mucin at the head of the
FG pathway
Msb2 is a FG pathway specific factor and part of the presumptive sensory complex
Cdc42 and Sho1 are recruited to the FG pathway by Msb2
The mucin domain of Msb2 inhibits its function
Msb2 is Secreted by the Exocyst Complex