1. Signal Transduction I Receptors & Ligands

2. Signal Transduction

3. Signal Transduction Pathway Overview agonists receptors 2 nd 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 2 nd messengers cAMP & DAG respectively These 2 nd 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 residues serve as binding motifs for transducer proteins

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

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. Secreted Signaling Molecules 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

18. Receptors for Soluble Signaling Molecules 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

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

20. Generalized Signal Transduction