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Signal Transduction I

Signal Transduction I. Receptors & Ligands. Signal Transduction. Signal Transduction Pathway Overview. agonists receptors 2 nd messengers cytoplasmic transducers/ effectors targets. The Usual Suspects. Seven Lively Helices. Seven-Helix Receptor Family.

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Signal Transduction I

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  1. Signal Transduction I Receptors & Ligands

  2. Signal Transduction

  3. Signal Transduction Pathway Overview • agonists • receptors • 2nd messengers • cytoplasmic transducers/effectors • targets

  4. The Usual Suspects

  5. Seven Lively Helices

  6. Seven-Helix Receptor Family • All 7-pass receptors interact with heterotrimeric G-proteins () • ligand binding triggers release of regulatory  subunits and GDPGTP exchange •  G-protein subunit then activates adenyl cyclase and phopholipases to produce 2nd messengers cAMP & DAG respectively • These 2nd messengers activate PKA and PKC respectively which phosphorylate targets and the C-term of 7-pass receptor

  7. Receptor Tyrosine Kinases

  8. Some Domains

  9. RTK Signaling • ligand binding induces dimerization • transphophorylation • phosphorylated residuesserve as binding motifsfor transducer proteins

  10. RTK- Ras Pathway GEF GAP Grb2,Shc GEF like Sos

  11. Jak Activation

  12. Receptor-JAK-Stat pathway

  13. Receptor S/T Kinases • Ligands are all members of TGF- superfamily

  14. Receptor Guanylyl Cyclases • binding of ligand induces guanylyl cyclase activity • These can be TM or cytoplasmic receptors • atrial natriuretic factor receptor is TM • NO receptor is cytoplasmic

  15. TNF Receptor Family • All transduce survival/death signals

  16. Juxtacrine Signaling: Notch Pathway

  17. FGF Family Hedgehog Family Wnt Family TGF Superfamily TGF Family Activin Family BMP Family EGF Family PDGF Family Retinoids HGF/Scatter Factor Neurotrophins Semaphorins Cytokines Secreted Signaling Molecules

  18. Receptor Tyrosine Kinase (RTK) pathway FGFR, EGFR, PDGFR Receptor coupled to ras signal transduction cascade Smad pathway Bipartite Serine/Threonine Kinase Receptors AcRI/II, TGFRI/II, BMPRI/IIs Receptors activate Smad transcription factors Wnt--catenin pathway Frizzled family of receptors Activation of pathway allows -catenin to enter nucleus JAK-STAT pathway Peptide hormone or cytokine receptor coupled to a Jak cytoplasmic tyrosine kinase Jaks activate STAT transcription factors Hedgehog Pathway Patched and smoothened co-receptors Activation of pathway converts Ci txn’l repressor to activator Steroids/Retinoids Nuclear/DNA binding receptors Hormone permits entry into nucleus, alters DNA binding conformation, or allows interaction with co-txn factors Receptors for Soluble Signaling Molecules

  19. ECM (ligand) Fibronectin Laminin Type IV collagen Integrins (receptor) CAMs (receptor) Cell Associated Signaling Molecules • Notch Family (receptor) • Delta Family (ligand) • Eph Family (receptor) • Ephrin Family (ligand)

  20. Generalized Signal Transduction

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