Cell Communication and

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??????
? ? ? ?
Cell Communication and Signal Transduction
2
? ?
???????
????? ??????
????? ???????????????????,?????????
3
????????
? ???????????
? ?????????????????????????
?????????????????????
4
???????????
???????????
????????????????
????????????
???????????????????
??????????
5

? ? ? ? ? ? ?

Signal Molecules
6
?????????

• ??
• ???????(extracellular signal molecules)
• ????????????????????????,????????

7
???? ??????(???????????????)
????????(???????????????) ?????(???????????)
?????(?????) ??(??????????)?
8
? ?
(?)????
????????(synaptic signal)
?? ???????? ??????????????? ???????
?? ????????????
9
(?) ?????
???????(endocrine signal)
?? ????????????? ??????????? ??????????
?? ??????????????
10

• ?????????????

???? ?????????? ?????? ????????????????
????? ?????????????

• ??????????

?????? ?????????? ?????? ?????????????
11
(?)??????
???????(paracrine signal?
?? ???????????
??????,?????????????? ?????????
?? ???????????
12
(?)????
?? NO??(NOS)????L-?????????NO
???????????????CO
13
??
???????????????????????????,???????(autocrine
signal)
?????????????????????,????????
14
? ?
?????????
???????(intracellular signal molecules)
???????????????????????????????
15
????
16
?????(secondary messenger)
??????????????,?Ca2?DAG?IP3?Cer?cAMP?cGMP???????
???????
?????(third messenger)
??????????????,???DNA????,??????????????????,?????
?????????(immediate-early gene)?????? ?
17
????????????????
?? ???? ?? ????????
???? ?????????? ???? ???? ????????
???? ???????? -1???????? ????????? ???? ???????????????????,????????????
?? ???????????????? ?????????? ???? ???? ?? ????
??? ???A????D ???? ??
? ?
18
? ? ? ? ?
Receptor
19
?????
????????????????????????????,?????????????????????
?????,???????????????,??????
??????????????????? ??(ligand)?
20
???????????????
??????
(?)???(membrane receptor)
???????????,????????????????????????????????????,
G?????????????
? ?
21
1. ???? ?????????
??????
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2. G ??????(G-protein coupled receptors,
GPCRs) ???????????/????(serpentine receptor)
G????????? ?????-??, N?????,C????????????
? ?
23
???????
???N??????????
????????????G-????? ?
?????????????????,???????????????
24
C-????????Cys????????a????????ß???????????????,?
??????????????
???C-????????????Thr?Ser???????,?????ß-???????
?(arrestin)?? ,????????G??????
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? G??(guanylate binding protein)
????GTP?GDP?????????????????,??????
??????? ????????????
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??G??????????????
? ?
27
H
??????
R
R
AC
AC
cAMP
GDP
ß
?
GTP
ATP
28
????????G??
29
?????????????
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3. ?????????
?TPK?????? EGF??????
IGF-1???????? PDGF?????????
FGF?????????
? ?
31
??????????(?????)
?????????????????,???????insulin growth factor
receptor, IGF-R?? ????????(epidermal growth
factor receptor, EGF-R)?
???????????
??????,??????????????????,??????????????
? ?
32
?????(autophosphorylation) ??????????????,?????(c
atalytic receptor)????????,???????????(tyrosine
protein kinase, TPK)???,????????????????,?????????
???
?????????????????????
33
????
???????????
??????2226??????????a-??,?????
??????????????(??SH1, Scr homology 1
domain,?Src???????????) ??C??,??ATP?????????????
34
?????????
SH2??? ???????????????? SH3??? ????????????
PH???(pleckstrin homology domain)
??????????????????,???G???ß?????? ,??????????
35
TGFß????????
? ?
36
4. ?????????????
??????????????? PKH??????
GC ?????????
? ?
37
(?)????(intracellular receptor) ?????????????,???D
NA?????
? ?????
?????
??N?,??????
??????
DNA???
??C?,??????????,??????,????
?????
???
38
????????
? ?
39
? ???? ???????????????
? ? ? ????????,?????????,??DNA?????????,???????
40
?????????
??-??????
41
?????????

• ??????????
• ?????????
• ??????
• G?????

42
? ? ?
???????
Signal Transduction Pathway
43
????????????

• cAMP- ??????

Ca2- ?????????

• cGMP- ??????

• ?????????

• ???? ???

• TGF-ß??

44
(?)cAMP - ????A??
??
??????,??,G??,?????? (adenylate cyclase,AC),
cAMP,???? A(protein kinase A,PKA)
45
1. cAMP ??????
46
?????? (adenylate cyclase,AC)
????? (phosphodiesterase, PDE)
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2.cAMP?????
PKA??? R ???? C ????
? ?
48
????A
(cAMP-dependent protein kinase,PKA)
cAMP
R
C
R
C
R ???? C ????
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3.PKA???
? ????????
?????????????,????????
50
???? ??
???? ?????
??G??
??AC
ATP
cAMP
????????????
? ?
51
(2) ??????????
?cAMP??????,????????????DNA??(TGACGTCA),??cAMP????
(cAMP response element , CRE)? ??cAMP????????
(cAMP response element bound protein,CREB)????????
??????
52
? ? ? ? ?
ATP
cAMP
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C
C
C R E B
???
C R E B
????
CRE
DNA
???
54
(No Transcript)
55
(?)Ca2-?????????

• 1. Ca2- ???????????

??
??????,G??
???C(phospholipase C, PLC)
????(diacylglycerol, DAG)
?????( inositol 1, 4, 5 triphosphate, IP3 )
????C(protein kinase C, PKC)
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(1) DAG,IP3????????
PLC
PIP2
DAG IP3
57
?PLC???????PIP2??DAG?,??????????DAG ?
???D (PLD)
???(PA)??
?????(PC)
DAG
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DAG,IP3? ? ?
IP3 ??????????????,????? Ca2??
DAG????????Ca2?????PKC
59
(2) PKC ????????

• ?????????????????(C1?C2?C3?C4 )????(V),??????????

60
Ca2 ????,?,?,
? ?
Ca2 ???? ?????????
61
PKC?????
? ???? ???PKC?????????? ?????????? ?????
?????????????

• ? ??????
• PKC ??????????????????

62
PKC ?????????????
? ?
63
2. Ca2-?????????????
( Ca2- CaM???? )
??

• ???G???PLC?IP3?Ca2??????CaM??

????(calmodulin , CaM) ???Ca2??????Ca2????CaM??,
??????????(????????)?
64
(?)cGMP-????G??
??
??,??????(guanylate cyclase, GC),cGMP, ????G
(protein kinase G,PKG)
cGMP??????
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PKG???
???????????????????
66
(?)?????????
? ?
???TPK(???????) ??????????????????(erb-B?
kit?fins?)?????
????TPK(????) ????JAK?????(src?yes?ber-abl?)???TPK
67
1. ???TPK-Ras-MAPK??
???????,GRB2, SOS, Ras??, Raf??,MAPK??

GRB2 (growth factor receptor bound protein 2)
SH2 ? (src homology 2 domain)
??????????????????,?????src?????????????,????????
?????????????
68
Ras????????,???G???G???
SOS (son of sevenless) ?????,??SH3??,??Ras?GDP??G
TP?
Raf?????/?????????
MAPK?? (mitogen-activated protein kinase)
??MAPK?MAPK??(MAPKK)?MAPKK??(MAPKKK),?????????????
? ?
69
????? EGF?PDGF?
???
?PTK?????
Ras-GTP
???
? ?
70
2. JAKs-STAT??
??
?????? JAKs (janus kinases) ???????????
(signal transductors and activators of
transcription ,STAT)
71
?????JAK?STAT??? ?????????????
? ?
72
(?)????B??

• ????B (nuclear factor- ?B, NF- ?B)

73
NF- ?B????????
? ?
74
?????????????????????????????,????????????????
75
(?)TGF-ß??
76

• SMAD??????TßR-??????,?Drosophila Mother against
  dpp (Mad)?C elegans (Sma)???????????
• ????9?SMAD,?????????
• ?????SMADs (receptor-regulated-SMAD,R-SMADs)
• ??????SMADs (common-partner-SMAD,Co-SMADs)
• ???SMADs (inhibitory-SMAD,I-SMADs)

77
?????????????

• ????
• ????
• ?????
• ??
• ?????
• ?????

78
??????????????????????
? ?
79

? ? ?
?????????
Cross Talk of Signal Transduction Pathways
80

• 1. ???????????????????????
• 2. ?????????????????????????????????????
• 3. ?????????????????

81

? ? ?
???????
Signal Transduction and Diseases
82
?????????LDL????
?????????? ????????????
?? ??????? ????G???????