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blood

3). 1). 2). blood. GF. R. A. B. C. D. E. HGF activation. Receptor families. a. Kinase N-terminal lobe. Receptor C-terminal tail. Lys 1110 (ATP/Mg ++ bind.). Catalytic loop. Asp 1204. Tyr 1234. Activation loop. Tyr 1235. Kinase C-terminal lobe. Ligand. P. P. P. P. P.

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blood

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  1. 3) 1) 2) blood GF R A B C D E Comoglio & Boccaccio

  2. HGF activation Comoglio & Boccaccio

  3. Receptor families a Comoglio & Boccaccio

  4. Kinase N-terminal lobe Receptor C-terminal tail Lys1110 (ATP/Mg++ bind.) Catalytic loop Asp1204 Tyr1234 Activation loop Tyr1235 Kinase C-terminal lobe Comoglio & Boccaccio

  5. Ligand P P P P P P P P P P P P P P P P Inactive receptor monomers Active tyrosine kinase Signal transduction Comoglio & Boccaccio

  6. Arg SH2 + _ P ----Tyr-----X------X-----hy---- Comoglio & Boccaccio

  7. SH2 SH2 PTPase P SH2 SH3 SH2 PH GAP PH P SH2 SH2 SH3 PLC Src SH2 SH3 Kinase P PLC- SH-PTP2 GAP STAT DNA bind. SH3 SH2 P Grb-2 SH3 SH2 SH3 Shc PTB P SH2 p85 PI3K SH3 Pro SH2 SH2 IRS-1 PH PTB P P P P P P P P Comoglio & Boccaccio

  8. Ras Ras GTP Ras SoS GDP Grb2 P SH2 PH plasma membrane Pi GAP GDP GTP RTK Multiple signalling pathways SH3 PolyPro Comoglio & Boccaccio

  9. Jun, ATF2 TCF Jun, ATF2 TCF Tyrosine Kinase Receptor ? Ras GAP PI-3K PDK Akt RalGEF Tiam1 Raf MEKK Rho GAP S6K Ral Rac MEK SEK Protein translation Rho ? MAPK/ERK SAPK/JNK PAK p38 TCF, Ets Protection from apoptosis Actin cytoskeleton rearrangements DNA transcription/Duplication Comoglio & Boccaccio

  10. Rb P Ras p21 p27 cyclinD cdk4 DNA duplication E2F Cell proliferation Comoglio & Boccaccio

  11. GDP Rac Ras GTP PIP2 PIP2 P P P P IP3 P Bad Ca++ SH2 PH plasma membrane P PTEN PI3K Tiam1 P PIP3 P PLC Actin cytoskeleton P P P p85 PDK P PAK PKC DAG Akt Cell migration ? P SAPK p38 P P S6K Raf P Protein synthesis DNA duplication Cell proliferation Cell survival Comoglio & Boccaccio

  12. SH3 SH3 Kinase SH2 SH2 YP KInase YP Y Inactive Active Comoglio & Boccaccio

  13. P P P P plasma membrane P MAPK P nucleus P STAT DNA Cell proliferation and/or differentiation Comoglio & Boccaccio

  14. TGF-, BMP, activin R2 R1 plasma membrane Serine-threonine kinase P Smad 4 Smad 6 P Smad 1,2 nucleus P Smad 1,2 Smad 4 X DNA Growth inhibition/differentiation Comoglio & Boccaccio

  15. 2 2 2 4 4 4 1 1 1 1 3 3 3 3 EGF Neuregulins 1-2 Figure 3.b Comoglio & Boccaccio

  16. PDGF AB PDGF BB PDGF AA       Figure 3.c Comoglio & Boccaccio

  17. Tyrosine kinase receptor Ras GAP Ras PI-3K Tiam1 Raf MEKK Rho GAP PDK Rac MEK SEK Akt Rho ERK/MAPK SAPK/JNK PAK S6K TCF-1, myc Jun, ATF2 cytoskeleton cytoskeleton DNA transcription/Duplication protein translation Comoglio & Boccaccio

  18. GTP plasma membrane P P Src PIP3 P Rac Ras GNEF SoS P P Raf PI3K GDP PDK P ? P Grb2 MEK p85 P P AKT P MAPK P cytoskeleton STAT ? P nucleus S6K P TCF P P DNA movement survival proliferation and/or differentiation SH2 SH3 PH PolyPro Comoglio & Boccaccio

  19. B&C unlimited Comoglio & Boccaccio

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