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Ras. REOVIRUS (Respiratory Enteric Orphan Virus)

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Presentazione sul tema: "Ras. REOVIRUS (Respiratory Enteric Orphan Virus)"— Transcript della presentazione:

1 Ras

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9 REOVIRUS (Respiratory Enteric Orphan Virus)

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13 CAAX X = Met, Ser, Cys X = Leu, Ile FTasi Zn Zn GGTasi I CX CXC GGTasi II Rab

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17 Zarnestra (Tipifarnib, R115777) Sarasar (Lonafarnib, SCH66336)

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19 EVIDENZE A FAVORE DI UN EFFETTO Ras-INDIPENDENTE PER GLI FTI mancanza di correlazione tra suscettibilità e status di Ras discrepanze nella cinetica con cui si sviluppano gli effetti inibizione di della crescita cellulare dipendente da K-Ras e N-Ras

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25 MAPK pathways MAPK, mitogen-activated protein kinase; MEK, MAPK kinase; ERK, extracellular signal-regulated kinase Stimulus MAPKKK MAPKK MAPK Biologic response AMLKs, TAK, ASK1 MKK3/6 P38 MAPK / MEKK1,4 MLKs ASK1 MKK4/7 SAPK/ JNK1,2,3 Inflammation, apoptosis, proliferation, differentiation Stress, inflammatory cytokines, growth factors Proliferation, differentiation, development, survival A-Raf, B-Raf, C-Raf Growth factors, mitogens ERK1/2 MEK1/2

26 MAPK pathways AMLKs, TAK, ASK1 MKK3/6 P38 MAPK / MEKK1,4 MLKs ASK1 MKK4/7 SAPK/ JNK1,2,3 Inflammation, apoptosis, growth, differentiation Stress, inflammatory cytokines, growth factors Stimulus MAPKKKMAPKKK MAPKKMAPKK MAPKMAPK Biologic response A-Raf, B-Raf, C-Raf Growth factors, mitogens ERK1/2 MEK1/2 Proliferation, differentiation, development, survival MAPK, mitogen-activated protein kinase; MEK, MAPK kinase; ERK, extracellular signal-regulated kinase

27 The role of MEK1/2 SHCGrb2SOS1 P P P Raf1 P MEK2 P MEK1 P Grb2, growth factor receptor-bound protein 2 Ras ERK2 ERK1

28 The role of MEK1/2 SHCGrb2SOS1 P P P Raf1 P MEK2 P ERK2 P P ERK1 P P MEK1 P Transcription factors Grb2, growth factor receptor-bound protein 2; SRF, serum response factor Ras SRF Transcription

29 Constitutive Ras-Raf-MEK-ERK activation Raf1 P MEK2 P ERK2 P P ERK1 P P MEK1 P SRF Ras Transcription

30 MEK1/2 inhibition SHCGrb2SOS1 P P P Raf1 P MEK2 P MEK1 P Ras MEK1/2 inhibition ERK2 ERK1


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