Istologia

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
Src
SH2
SH3
Kinase
P
PLC-?
SH-PTP2
GAP
STAT
P
SH3
SH2
DNA bind.
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
plasma membrane
Pi
GAP/NF1
GDP
GTP
RTK
Multiple signalling pathways
SH3
PolyPro
9
Point mutation in the GTPase domain
plasma membrane
Pi
GAP
GDP
GTP
RTK
constitutive activation
Multiple signalling pathways
CANCER !
10
Tyrosine Kinase Receptor
?
Ras
GAP
PI-3K
PDK
Akt
Tiam1
RalGEF
Raf
MEKK
Rho GAP
S6K
Rac
Ral
MEK
SEK
Protein translation
MAPK/ERK
SAPK/JNK
Rho
PAK
?
p38
TCF, Ets
Protection from apoptosis
Actin cytoskeleton rearrangements
DNA transcription/Duplication
11
Ras
Myc
p21
p27
cyclinD
cdk4
DNA duplication
E2F
Cell proliferation
12
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13
(No Transcript)
14
plasma membrane
P
PTEN
PI3K
Tiam1
P
PIP3
P
PLC?
Actin cytoskeleton
P
P
P
p85
PDK
P
PAK
PKC
Akt
DAG
Cell migration
?
P
SAPK
p38
P
P
S6K
Raf
P
Protein synthesis
DNA duplication
PH
Cell survival
Cell proliferation
15
plasma membrane
P
MAPK
P
nucleus
P
STAT
DNA
Cell proliferation and/or differentiation
16
I segnali anti-proliferativi
G0
GZ
Differentiation
Quiescent
Post-mitotic
Cell cycle
17
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
18
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
19
Il cancro è una malattia dei tessuti
20
(No Transcript)
21
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