Membrane Function Signal Transduction. I. Introduction to Receptors & Signal Transduction.
Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.
-
Upload
frank-ford -
Category
Documents
-
view
230 -
download
2
Transcript of Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.
![Page 1: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/1.jpg)
Chapter 15
Cellular Signal Transduction
The biochemistry and molecular biology department of CMU
![Page 2: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/2.jpg)
2. Intracellular receptor (transcription regulated recepto
r) Intracellular R is trans-acting
elememt cis-acting element gene expression
Localized in the cytosol and/or in the nucleus.
ligand: Steroid H, VD3, Thyroxine
![Page 3: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/3.jpg)
![Page 4: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/4.jpg)
3. Properties of binding of H and R
• highly specificity
• highly affinity
• saturation
• reversible binding
• special function model
![Page 5: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/5.jpg)
4. Control of receptor activity
• Phosphorylation or dephosphorylation of R
• Phospholipid of membrane
• Enzyme catalyzed hydrolysis
• G protein regulation
![Page 6: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/6.jpg)
(1) Recognize the special ligand
(2) Binding to special ligand
(3) Signal transduction biological effect
5. Function of receptor
![Page 7: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/7.jpg)
§3 Pathway of Signal
Transduction
![Page 8: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/8.jpg)
Signal transduction mediated by membrane receptor
• cAMP dependent-protein kinase A pathway
• cGMP dependent PKG pathway • Ca2+ dependent PK pathway • Tyrosine protein Kinase pathway
• NF-κB pathway • TGF- βpathway
![Page 9: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/9.jpg)
1. cAMP dependent-protein kinase A pathway
H R
G protein
Phosphorylation of Es or functional proteins
Biological effects
PKA
cAMPAC
![Page 10: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/10.jpg)
(1) cAMP metabolism
ATPMg2+
PPi
cAMP
H2OMg2+ 5'-AMP
AC PDE
AC : Adenylate cyclase
PDE : Phosphodiesterase
![Page 11: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/11.jpg)
PDE
H2O
N
N N
N
NH2
O
H
OHOH
CH2
H
H H
OPO
O
O
PO
O
O
P
O
O
O ATP
ACPPi
N
N N
N
NH2
O
H
OHO
CH2
H
H H
O
PO
O
cAMP
N
N N
N
NH2
O
H
OHOH
CH2
H
H H
OPO
O
O
5'-AMP
![Page 12: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/12.jpg)
(2) Mechanism of cAMP effect
Activate cAMP-dependent protein kinase (PKA).
![Page 13: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/13.jpg)
![Page 14: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/14.jpg)
(3) PKA effect
![Page 15: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/15.jpg)
![Page 16: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/16.jpg)
Phosphorylate specifically Ser/
Thr residues in several proteins
( 1 ) Regulation of metabolism
( 2 ) Regulation of gene e
xpression
![Page 17: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/17.jpg)
hormons: glucagon, epinephrine
inactive AC active AC
ATP cAMP
inactive PKA active PKA
phosphorylase b kinase
phosphorylase b kinase
P
ATP
ADP
H2O
Pi
phosphorylase b
P
P
ATP ADP
Pi
H2OATP ADP
glycogen synthase
glycogen synthase
P
H2OPi protein phosphatase-1
(active) (inactive)
inhibitor-1 (active)
inhibitor-1 (inactive)
phosphorylase a
ATP
![Page 18: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/18.jpg)
CRE : cAMP response element (T
GACGTCA)
CREB: CRE binding protein
![Page 19: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/19.jpg)
DNACRE
CREB
PKA
P
Transcription
mRNA
CREB
PKA
P
CREBP
CR
EBP
CR
EB
P
CREBP
CR
EB
P
CR
EB
P
![Page 20: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/20.jpg)
![Page 21: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/21.jpg)
2. Ca2+ dependent PK pathway
(1) Ca2+ -DAG -dependent PKC pathway
H R
PIP2
G protein PLC
IP3 DG
ERPKC
Ca2+ PS
Biological effects
Phosphorylation of Es or functional proteins
![Page 22: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/22.jpg)
![Page 23: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/23.jpg)
[Ca 2+]i 0.01-1 mol/L ( 10-7 mol/L )
[Ca 2+]o 2.5mmol/L ( 10-3 mol/L )
5000~10000×
![Page 24: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/24.jpg)
1 ) Function of DG and IP3
IP3 + R→open of Ca2 + channel →[Ca2 + ]↑
PS, Ca2 +DG PKC ↑
![Page 25: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/25.jpg)
![Page 26: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/26.jpg)
2 ) Function of PKC
• regulation of metabolism
PKC →Ser/Thr-P of R, enzyme,
Protein of Mb.
• Gene expression
![Page 27: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/27.jpg)
Late response:
Trans-acting factor-P
Third messengerImmediate early genes
Third messenger-P
Activate genes
Cell proliferation
PKC
PKC
Early response:
![Page 28: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/28.jpg)
![Page 29: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/29.jpg)
(2) Ca2 + -CaM dependent protein kinase pathway
H R G protein PLC
IP3
Ca2+ CaM
CaMK
Biological effects
Phosphorylation of Es or functional proteins
![Page 30: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/30.jpg)
Calmodulin (CaM ): Ca2 + binding protein
4 Ca2 + + CaM → Ca2 + - CaM
↓ CaM kinase↑
↓ Ser/Thr - P ↓
Ca2 + pump, AC ↑ GC ↑
Es (glycogen synthase, phosphorylase kinase)
![Page 31: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/31.jpg)
![Page 32: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/32.jpg)
![Page 33: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/33.jpg)
3. cGMP-dependent PKG pathway
Biological effects
Phosphorylation of Es or functional proteins
ANPNO, CO
Soluble GC
PKG
cGMPReceptor-linked GC
![Page 34: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/34.jpg)
(1) cGMP
(2) Function of PKG
Ser/Thr- P of protein and E
Mg2+
PPi H2O
Mg2+GTP cGMP 5'-GMP
GC PDE
GC: Guanylate cyclase
![Page 35: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/35.jpg)
ANP ( atrial natriuretic peptides ) ↓
GC NO
↓
cGMP
↓
PKG
↓
Vascular dilatation
![Page 36: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/36.jpg)
cis-acting elementnucleus
expression
cell memberane
phosphorylation of enzymes or proteins effects
CaM-PK
Ca2+-CaMCa2+
IP3DGcAMP cGMP
PKA PKG PKC
ATP GTP PIP2(PC)
G AC GC G PL
peptide hormonesneurotransmitters AFP
neurotransmittershypothalamic pituitrin
Ptrans-acting factor
![Page 37: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/37.jpg)
4. Tyrosine-protein kinase pathway (TPK)
• TPK receptor is related to proliferation, differentiation, dissociation, carcinomatous change.
• TPK:receptor TPK : Mb.
non receptor TPK : cytosol
![Page 38: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/38.jpg)
(1) Receptor TPK - Ras - MAPK pathway
• GRB2, SOS, Ras, Raf
• Small G protein: Ras
• MAPK (mitogen-activated protein kinase):
MAPK、MAPKK、MAPKKK
![Page 39: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/39.jpg)
ÊÜÌå ÐÍTPKϸ°ûĤ
EGF, PDGF
receptor TPK Ras - GTPSOS - PGRB2 - P
Raf - P
MAPKK - P
MAPK - Ptrans-acting factor
expression
nucleus
- P
![Page 40: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/40.jpg)
(2) JAKs - STAT pathway
ligand
non TPK receptor
JAKs STAT
gene expression
![Page 41: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/41.jpg)
• JAKs
• STAT: Signal transductors and activa
tor of transcription
![Page 42: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/42.jpg)
ÖÊĤ
¸ÉÈÅËØÓ¦´ð Ôª¼þ
ºËĤ
»ùÒò
£ PP£
JAK
11391
84
48
113
P
91P 84 P
48
113
91 84P P
P
interferons
inactive STAT
Plasma membrane
STAT complex
Nuclear membrane
geneInterferons response element
transcription
![Page 43: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/43.jpg)
![Page 44: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/44.jpg)
![Page 45: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/45.jpg)
Dimerization of Receptor
Interferon
Autophosphorylation of JAK
Phosphorylation of STAT
Nuclear translocation of STAT
Interferon response element
Expression of gene
![Page 46: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/46.jpg)
5. Nuclear factor-κB pathway
![Page 47: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/47.jpg)
6. TGF-βpathway
![Page 48: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/48.jpg)
Intracellular receptor (DNA transcription regulated
receptor)
• Steroid H, VD3, Thyroxine
• Cytosolic R: glycocorticosteroid H
• Nuclear R: thyroxine, estrogen, androgen, progesterone
![Page 49: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/49.jpg)
![Page 50: Chapter 15 Cellular Signal Transduction The biochemistry and molecular biology department of CMU.](https://reader034.fdocuments.us/reader034/viewer/2022052223/5697c0271a28abf838cd608e/html5/thumbnails/50.jpg)
Serum binding proteinWith bound bormone