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Download Cullen Lecture 6: Signal Transduction in Fungi Filamentous Growth
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Transcript
Cullen Lecture 6: Signal Transduction in Fungi Filamentous Growth Saccharomyces cerevisiae (G . Fink) And fungal pathogens Specificity of Signaling Pathways Containing Cdc42 and MAPK Components in Yeast Signal Transduction Pathways Control Fungal Behavior Stimulus Signaling Response Nucleus Cell Receptor New Cell Type Filamentous Growth Pathway FGP Receptor: ? GTPase/PAK: Cdc42/Ste20 MAPK3: MAPK2: MAPK: Ste11 Ste7 Kss1 Txn1/Txn2: Ste12/Tec1 Yeast Signaling Proteins are Homologous to Mammalian Counterparts “Cross-Talk” in Signaling Pathways http://www.hhmi.org/research/investigators/wu.html Prediction of Specificity Factors FGP Sho1 + ? Cell Wall Cdc42/Ste20 Membrane Ste11 Ste7 Kss1 Ste12/Tec1 ? 42 Ste20 Sho1 Characterize the Msb2 Protein Msb2 is an Integral Membrane Protein Msb2 is glycosylated Topology of Msb2 Msb2 Cell Wall Glycosylated Cell Surface Plasma Membrane Integral Membrane Msb2 Ste20 42 Sho1 Topology and Domain Structure of Msb2 Glycosylation Sites 100 AA Signal Sequence Mucin-Homology Domain MembraneSpanning Domain Extracellular Cytoplasmic Msb2 is a Mucin Msb2 Cell Wall MucinHomology Domain Plasma Membrane Mucins are Gross but Important Mucins in Mammalian Cells Disease resistance Metastasis Signaling role MUC1 and MUC4 Docks ß-catenin Grb2-Sos-Ras-MEK-ERK2 pathway Erb2/Her2/Neu Erb2-Erb3 Msb2’s Mucin-Homology Domain 100 AA N…(698)S Q V S D T S VSYTTSSSSVSQVSDTP VSYTTSSSSVSQVSDTP VSYTTSSSSVSQVSDTP VSYTTSSSSVSQVSDTP VSYTTSSSSVSQVSDTS VPSTSSSSSVSQVSDTP V P S T S S S S S V S Q (818) …C Is the Mucin Domain Required for FG Pathway Activity? wt Dmucin Msb2 w/o the Mucin Domain is Hyperactive Mucin Repeats Are Inhibitory Analysis of the Mucin Repeats (Continued) Repeats are Homologous at the Nucleotide Level Undergo Recombination-Mediated Deletion Msb2-Dependence of MAPK Specificity FGP PRP Msb2 Receptor Kss1 Fus3 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 The mucin domain of Msb2 inhibits its function Cdc42 and Sho1 are recruited to the FG pathway by Msb2 Msb2 is a FG pathway specific factor and part of the presumptive sensory complex Msb2 is Secreted by the Exocyst Complex
