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Istologia

Istologia. Corso di Laurea in Medicina e Chirurgia - A.A. 2002-03. Lezione 4. 11 Marzo 2003. 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. Kinase N-terminal lobe. Receptor

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Istologia

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  1. Istologia Corso di Laurea in Medicina e Chirurgia - A.A. 2002-03

  2. Lezione 4 11 Marzo 2003

  3. 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

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

  5. Arg SH2 + _ P ----Tyr-----X------X-----hy----

  6. 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

  7. Il cancro è una malattia dei tessuti

  8. Ras Ras GTP Ras SoS GDP Grb2 P SH2 PH plasma membrane Pi GAP/NF1 GDP GTP RTK Multiple signalling pathways SH3 PolyPro

  9. Ras Ras Point mutation in the GTPase domain plasma membrane Pi GAP GDP GTP RTK constitutive activation Multiple signalling pathways CANCER !

  10. 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

  11. Rb P Ras Myc p21 p27 cyclinD cdk4 DNA duplication E2F Cell proliferation

  12. GDP Rac Ras GTP PIP2 PIP2 P P P P IP3 P Bad Ca++ SH2 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 PH Cell proliferation Cell survival

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

  14. I segnali anti-proliferativi G0 GZ Differentiation Quiescent Post-mitotic Cell cycle

  15. cyc cdk 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 Myc p15 Growth inhibition/differentiation

  16. cyc cdk 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 Myc p15 Growth inhibition/differentiation

  17. Il cancro è una malattia dei tessuti

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