Cullen Lecture 6: Signal Transduction in Fungi. Filamentous Growth Saccharomyces cerevisiae (G....
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Transcript of Cullen Lecture 6: Signal Transduction in Fungi. Filamentous Growth Saccharomyces cerevisiae (G....
Cullen Lecture 6:Signal Transduction in
Fungi
Filamentous GrowthFilamentous Growth
Saccharomyces cerevisiae (G . Fink)And fungal pathogens
Specificity of Signaling Pathways Containing
Cdc42and MAPK Components
in Yeast
Signal Transduction Pathways Control Fungal Behavior
Stimulus Response New Cell TypeSignaling
Cell
Nucleus
Receptor
FGP
?
Cdc42/Ste20
Ste11Ste7Kss1
Ste12/Tec1
Filamentous Growth Pathway
Receptor:
GTPase/PAK:
MAPK3:MAPK2:MAPK:
Txn1/Txn2:
Yeast Signaling Proteins are Homologous to Mammalian
Counterparts
http://www.hhmi.org/research/investigators/wu.html
“Cross-Talk” in Signaling Pathways
Prediction of Specificity Factors
Sho1Ste2042
??
Cell Wall
Membrane
FGP
Sho1 + ?
Cdc42/Ste20
Ste11Ste7Kss1
Ste12/Tec1
Characterize the Msb2 Protein
Msb2 is glycosylated
Msb2 is an Integral Membrane Protein
Msb2
Topology of Msb2
Cell Wall
Plasma Membrane
Glycosylated
Integral Membrane
Cell Surface
Ste2042
Msb2
Sho1
Topology and Domain Structure of Msb2
Mucin-HomologyDomain
SignalSequence
Membrane-SpanningDomain
100 AA
Extracellular Cytoplasmic
Glycosylation Sites
Msb2
Msb2 is a Mucin
Cell Wall
Plasma Membrane
Mucin-HomologyDomain
Mucins are Gross but Important
Mucins in Mammalian Cells
Disease resistance
Metastasis
Signaling role
MUC1 and MUC4
Docks ß-cateninGrb2-Sos-Ras-MEK-ERK2 pathway
Erb2/Her2/NeuErb2-Erb3
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
wt mucin
Msb2 w/o the Mucin Domain is Hyperactive
Is the Mucin Domain Required for FG Pathway Activity?
Mucin Repeats Are Inhibitory
Repeats are Homologous at the Nucleotide Level
Undergo Recombination-Mediated Deletion
Analysis of the Mucin Repeats (Continued)
Msb2-Dependence of MAPK Specificity
PRP
Receptor
Fus3
FGP
Msb2
Kss1
Msb2 induces Kss1~P but not Fus3~P
Msb2 induces Kss1~P but not Fus3~P
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