Chapter 5

1 2 G3 4 5

Cell Communication

Cell Communication, , ,, P167

5.1.1

5.1

Cell signaling , , Signal transduction (), ,

5.1.2 Signal molecules P169

1. : 80

2. (paracrine signaling

2. (autocrine) (autocrine signaling) , , ,

3. (neurotransmitters) (synapses)

5.1.3 Receptor ( receptor)(ligand)

-

DNA

DNA N ,C

(ion-channel linked receptor)G-(G-protein linked receptor)(enzyme-linked receptor)

G-

Ion-channel linked receptor , , ,

G- G-protein linked receptor7G 1000G-, G-

G-

G

(catalytic receptor)(enzyme linked receptor)

P177(tyrosine kinase-linked receptors) (receptor with intrinsic enzymatic activity )

(Receptor tyrosine kinase)/ (Receptor serine/threonine kinase) (Receptor guanylyl cyclase) (Receptor of tyrosine phophatase);

.

: 7 :

(receptor crossover) 5.1.4

-(Kd) 10-9 M

5.1.5

(signaling cascade)

DNA

(second messengers)

:

:

cAMP cGMP 12-(DAG) 145-(IP3) Ca2+

5.2 G

G-:: , , , : GTPase; ADP5.2.1 G

G G; GG G(G protein cycle)

GTPase(GTPase-activating proteinGAP) GTP (guanine nucleotide-exchange factorsGEF) GDPGG (guanine nucleotide-dissociation inhibitorsGDI) GDPG GDIG G:

GTPaseGAP GEF GDI

GcAMPA

5.2.2 PKA(protein kinase A system PKA)

G7() G (effector) 5.2.2.1

G:G(membrane-bound machinery)

5.2.2.2 GG

G

ATPcAMPACG6

5.2.2.3 :cAMP (adenylate cyclase AC)

cAMP

cAMP cAMP

Gup regulation) down regulation)5.2.2.4cAMP

GcAMP G

(Stimulate Receptor Rs)() 7G Gs proteins cAMP

(Inhibite Receptor Ri) (Ri)GicAMPG(Gi-proteins) cAMP

cAMPA (cyclic-AMP dependent protein kinase A)

AATP 5.2.2.5 A (protein kinase APKA)

()

AcAMP

5.2.2.6 A PKA

GATPcAMPcAMPcAMPA(allsoteric site)A A:

1- 3. PKA

PKACREB(cAMP response element binding cAMP)CREBDNA (gluconeogenesis) A:

:

cAMP(cAMP phosphodiesterasePDE)cAMP5-AMP

cAMP RiGiGiGTPGiGiGiGiGiGs 5.2.2.7 cAMP

5.2.2.8 G G(ADP-ribosylation)GTPaseGTPGscAMPNa+

(pertussis toxin) GADPGiGDPGTP cAMPcAMP

5.2.3 PKC(protein kinase C system) CGqPIP2DAGIP3IP3Ca2+C

: 1. :G 7() 2. GqGTP/GDP cAMPG 3. C 5.2.3.1

:IP3DAGCa2+ :C IP3/DAG Ca2+

5.2.3.2

C- GqGq-C-C- IP3/DAG C-(PIP2) (IP3)(DAG)

IP3 Ca2+ IP3 IP3IP3 IP3-Ca2+ Ca2+

5.2.3.3 C

5.2.3.4 CPKC PKC;CA A

5.2.3.5 Ca2+(calcium ions) Ca2+Ca2+10-7MER Ca2+ 10000

Ca2+ERCa2+ER Ca2+Ca2+ Ca2+ p204

(calmodulin) 148Ca2+ Ca2+ 4Ca2+

Ca2+- -Ca2+-CaM-cAMPCa2+(P119)

5.2.3.6 IP3/DAG/Ca2+ DAG DAG :DAG,(PA),PACMP-,(PI)DAG DAG ,

IP3IP35-I(14)P2 3-IP3ATP-1345-(IP4) IP3 IP3

IP4Ca2+ , Ca2+ Ca2+, Ca2+-ATP Ca2+Ca2+(10-7 M),CaM-,, Ca2+

5.3 (signaling via enzyme-linked receptor) (G-) ()

GTPcGMP; cGMPcGMPGG ;cGMP5.3.1 cGMP

PKGGCGC

RTKs(receptor tyrosine kinase) Rasc-rasRTKs/Ras5.3.2 /Ras

5.3.2.1

5.3.2.3 Insulin receptor substrate IRS

IRSsIRSsSH2

Src(Src homology domain)(SrcRous )SH2100SH350 SH(SH domain)

Epidermal growth factor receptor EGF EGF ,EGF5.3.2.4

EGFEGF

EGF()SH2()

Ras(Ras protein)c-ras Ras(rat sarcoma) GTP GTPGTPGDP5.3.2.5 Ras

GTPase

Grb2(growth factor receptor-bound protein 2)Sos

Grb2Sos,SosSosRas,Grb2SH2SH3,SH SosRas

p218MAPK

EGFGrb2-SosGrb2-SosSosSosRasGDP GTPRas P217 RasP218 Ras

RTKs/Ras

RTKs Grb2-Sos RasRafMAPKKKMAPKKMAPK()

NO5.4 5.4.1 NO

NO

5.5 5.5.1

(convergent )

(divergence )

PKA (crosstalk)

In actual fact, signaling pathways in the cell are much more complex.

cAMPIP3DAG5.5.2 (termination)

(receptor down-regulation), ,,, (receptor desensitization),, ,

1G ( ) A GDP, B GTP, C GTP, D GDP, 2GcAMP A cAMP B G C D GAC PKAG A22

1. PKAPKC2. Describe the similarities and differences in the cycling of Gs and Ras between the active and inactive forms.

1. , :()2. G, PKAPKC, , G3. , , /Ras, Ras4. , ,G