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Cullen Lecture 6: Signal Transduction in Fungi

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. New Cell Type. Stimulus. Signaling. Response.

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Cullen Lecture 6: Signal Transduction in Fungi

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  1. Cullen Lecture 6: Signal Transduction in Fungi

  2. Filamentous Growth Saccharomyces cerevisiae (G. Fink) And fungal pathogens

  3. Specificity of Signaling Pathways Containing Cdc42 and MAPK Components in Yeast

  4. New Cell Type Stimulus Signaling Response Signal Transduction Pathways Control Fungal Behavior Nucleus Cell Receptor

  5. FGP ? Cdc42/Ste20 Ste11 Ste7 Kss1 Ste12/Tec1 Filamentous Growth Pathway Receptor: GTPase/PAK: MAPK3: MAPK2: MAPK: Txn1/Txn2:

  6. Yeast Signaling Proteins are Homologous to Mammalian Counterparts

  7. “Cross-Talk” in Signaling Pathways http://www.hhmi.org/research/investigators/wu.html

  8. FGP Sho1 + ? Cdc42/Ste20 Ste11 Ste7 Kss1 Ste12/Tec1 Prediction of Specificity Factors Cell Wall Membrane ? 42 Sho1 Ste20

  9. Characterize the Msb2 Protein Msb2 is an Integral Membrane Protein Msb2 is glycosylated

  10. Msb2 Glycosylated Cell Surface Integral Membrane Topology of Msb2 Cell Wall Plasma Membrane

  11. Sho1 Msb2 42 Ste20

  12. Glycosylation Sites 100 AA Membrane- Spanning Domain Signal Sequence Mucin-Homology Domain Extracellular Cytoplasmic Topology and Domain Structure of Msb2

  13. Msb2 Mucin- Homology Domain Msb2 is a Mucin Cell Wall Plasma Membrane

  14. Mucins are Gross but Important

  15. Signaling role MUC1 and MUC4 Docks ß-catenin Grb2-Sos-Ras-MEK-ERK2 pathway Erb2/Her2/Neu Erb2-Erb3 Mucins in Mammalian Cells Disease resistance Metastasis

  16. N…(698)S Q V S D T S V S Y T T S S S S V S Q V S D T P V S Y T T S S S S V S Q V S D T P V S Y T T S S S S V S Q V S D T P V S Y T T S S S S V S Q V S D T P V S Y T T S S S S V S Q V S D T S V PS T S S S S S V S Q V S D T P V PS T S S S S S V S Q (818) …C Msb2’s Mucin-Homology Domain 100 AA

  17. Is the Mucin Domain Required for FG Pathway Activity? Dmucin wt Msb2 w/o the Mucin Domainis Hyperactive

  18. Mucin Repeats Are Inhibitory

  19. Analysis of the Mucin Repeats (Continued) Repeats are Homologous at the Nucleotide Level Undergo Recombination-Mediated Deletion

  20. FGP Msb2 PRP Receptor Fus3 Msb2-Dependence of MAPK Specificity Kss1

  21. Msb2 induces Kss1~P but not Fus3~P

  22. Msb2 induces Kss1~P but not Fus3~P

  23. 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

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