1. G (GPCRs)

2. 3. 4.

a+

Ca2+

K+

a+/K+-ATP

-

4

1004

4

GPCR

1. 2. 3. 4.

1.

G

, GPCRs

4

,

4.1 Rs ), 1

GPCRs)

GPCRs .

,

( 45% .

.

(>1.0

350

,

.0%). 28 ,

G .

G

1%

000) -

)

%

.

: (G

G

. Richard

(

GPCRs).

.

(G prote

2.000

d Axel ( GPCRs

( .

,

/ /

ein-couple

. Nobe

,

. .

ed recepto

GPCR-like

, el 2004)

,

ors:

e

105

, . 150 , .

, , , , GPCRs . GPCRs : 30%40% 50 400 GPCRs.

2012 Nobel Brian Kobilka Robert Lefkowitz GPCRs.

Brian Kobilka (1955 - ) Robert Lefkowitz (1943- )

4.2 Brian Kobilka Robert Lefkowitz Nobel

GPCRs. 1968, Lefkowitz -

, 1980 Kobilka . - . 2011, Kobilka - . molecular masterpiece.

GPCRs: :

.

106 4

( GPCRs) 11-cis- () trans-.

: .

: , , , , GABA.

: , .

: GPCRs, , , .

: . .

GPCRs,

G (, ), (effectors) (cAMP, I3), . GPCRs .

- GPCRs 3 ( 4.3 4.4).

, , , GPCRs ( , , , ), GPCRs (fMLP-peptide, PAF, ), , (, , ), (LH, TSH, FSH) GPCRs. ( 4.3 ), 1 2 , .

, NH2 , , . , , . , , , VIP , NH2-.

C, , Ca2+ GABAB. 2- COOH-. 2 , .

107

1 2 , .

4.3 - (, , C) GPCRs . Strosberg and Nahmias, G-protein coupled receptor signaling through protein networks, Biochemical Society Transactions, 2007, 35, 23-28.

C

108 4

4.1 GPCRs , .

(((777000222)))

1: (CCR1- CCR8)

2: (CXR3- CCR7), -8 (IL8-R)

3:

4: (delta, kappa, mu ) (SSTR1-5)

5: (GALR1-3)

6: (CCKAR), , , GnRH (Gonadotropin releasing hormone)

7: TRH (Thyroptropin-releasing hormone)

8: fMLP (Frmyl Met-Leu-Phe peptide)

9: , , (neuropeptide Y), PRP (prolactin releasing peptide)

10: (LH, TSH, FSH)

11: (P2RY1-8)

12: (P2RY12-14)

13: (CNR), (LPAR1-3), ,

14: (: PGD2, PGE1, PGE2, PGE3, PGE4, PGFF, PGI2, A2)

15: (LPAR4-6), (2R-10)

16: ( 1-5)

17: (5-2, 5-2B, 5-2C, 5-6) , () (1, 1, 1D, 2A, 2B, 2C, 1, 2, 3), (D1 D5), (2)

18: (1, 3, 4), (1, 2a, A2b, A3), (1-5)

GPCRS A

GPCRs . 400 600 7 . 7 - ( 20-25 ), 3 - (loops) 3 . , .

3

(

C

.

G 2- COOH-

.

,

,

S1M

. , ),

.

4.4 A- . Strosberg an17, 373-381.. Malbon, Phys

, (PK

G

A. . COOH

and F. Pietri-1. GPCsiological Re

. , G

Ser

KA, PKC

( 2 , . D. -Rouxel, TiPS

CR. Moev. 1999.

S-S,

r Thr, GRK),

1

),

3

PS, 1996,

orris and

.

109

110 4

. G -.

4.5 . - (binding pocket).

A C.D. Strader et al, Faseb J., 1989, 3, 1825-32. . , , Zubay G, Biochemistry 1998.

4.6 . 3-, .

sp117 3 , (Ser209 Ser212) 5 Phe309 6 . ( ). e1-e4: 4 , i1-i3: 4 . D. Strosberg and F. Pietri-Rouxel, TiPS, 1996, 373-381.

. - . Berg et al, 2001.

, (binding site) .

1. (, , , , , ) . - ( sp 113: 113 2- ).

A. B.

A.

111

(COO-) (counter-ion) (2+) . , , . , 3, Ser209 Ser212 V (...) +, -. (binding pocket).

2. , , , . , . 70 - GPCRs, (PARs: proteinases-activated receptors). , , - . - , - , .

4.7 PARs (

). , , 2- , 2- , . Vergnolle N., et al, Proteinase-activated receptors: novel signals for peripheral nerves, Trends in Neurosci. 2003, 26, 496-500. 3. ,

30 kDa -, , -, (FSH: follicle stimulating hormone), (LH: lutropin), (hCG: human chorionic gonadotropin), (350-400 ) , . 2- , 20-25 - -, . 2- 9 , .

112 4

4.8 . 2 (ectodomain) -, 7 (7TM) (IC) 3 C-.

4.9 1 , -. , -.

2 PARs , N2-, .

3 , 2-, .

1 ,

2 8 (IL8) fMLP- PAF

3 (LH, TSH, FSH)

113

4.10 GPCRs. , .

GPCRs,

. , .

GPCRS A ,

. H1, H2, H3 H4.

H1 , , , . G (Gq), C PIP2. H1 , .

, 1 ( 2). 1- . , 1 . , . , , ,

3

(LH, TSH, FSH)

2

()

2

,

1 ,

,

114 4

, , .

4.11 1

, . , . , .

H1- , Daniel Bovet (1933), , Institut Pasteur . Bovet 1957 Nobel. 1 Benadryl () Johnson & Johnson 1946. , ( ) .

2 H1 ( 1 , ). , . pH (7.4) , . 2 H1 . 1993 Schering-Plough (. Claritin). 2 , , , Zyrtec Pfizer.

3 (levocetirizine) (desloratadine & fexofenadine) 2 , , .

H2 ,

, . , 2 . H2- , . H2

115

, .

4.12 , G , . 1, Gaq , C Ca2+. 2, Gas , cAMP. 3 4, Gai , + Ca2+. R. Ferstl, C. Akdis, L. O'Mahony, Histamine regulation of innate and adaptive immunity. Frontiers in Bioscience, 2012, 17, 40-53.

o H2 Sir James

Black Smith, Kline and French 1960 Tagamet 1976. , - . Glaxo , 2- ( , 10 , 10% CYP450 ). 1981 Zantac, 1988, 2-, , 2- CYP450 . Johnson & Johnson/Merck Pepcidine.

116 4

H3 (H3R) H4 (H4R) 1988 2000, , , . H3R , H4Rs , , . H3Rs , , , , . H3R II. H4R , , .

GPCRS A , 5- (5-R),

GPCRs (5-1, 5-2, 5-4, 5-5, 5-6, 5-7), 5-3 - . , , , , , , , , , , . GPCRs 5 , , . :

buspirone 5-HT1A. 1986 Bristol-Myers Squibb BuSpar (GAD, generalized anxiety disorder). buspirone , .

(lecozotan) 5-1, Wyeth Alzheimer. 5-1 . 2008, III .

(sumatriptan) , - (DMT), 5---, (5--).

4.13 , , 5-

HT1D 5-HT1B, .

117

4.14 Albert Hofman

(1906-2008) , LSD. 100 , LSD: My Problem Child.

5-HT1D 5-HT1B, . : / , / / . 15 min 96% . GlaxoSmithKline Imitrex 1991 .

(cisapride) 5-HT4, . (gastroprokinetic) . Janssen Pharmaceutica 1980, Prepulsid, , . , (), .

(agomelatine) 5-HT2C , , , . Novartis, 2012, Valdoxan, . , .

(fenfluramine) 5-HT2C 1972 Ponderax,

. , .

LSD (Lysergic acid diethylamide) Sandoz , Albert Hofmann 1938, . , (ergot), . , 1943. LSD , . Sandoz, Delysid, 1947, . LSD GPCRs, , , 5-HT2A, 5-HT2A . 5-HT2A 5- .

118 4

LSD, , 5-2 ( D2 ).

4.15 ( -

) .

GPCRS A GPCRs

. 5 , GPCRs: D1, D2, D3, D4, and D5. D1 D5 D1-like, D2, D3 and D4 D2-like. , , , , , .

(, ), . , Parkinson, (restless legs syndrome, RLS)1.

1 (), , . , . .

Fenfluramine

119

(ropinirole) D2, D3, D4 D2. GlaxoSmithKline Requip Parkinson Restless Legs Syndrome (RLS). SSRI (serotonin specific reuptake inhibitors) .

(apomorphine) D1-like and D2-like . , , .

4.16 , ,

HCl, Parkinson. .

Parkinson (1951), (1970), . . Parkinson Apokyn, . Uprima, Viagra, . -, Alzheimer. .

(aripiprazole) 2 , , , . 2002, 2004, 2007. Otsuka Aripiprex. , D2 , .

(risperidone) , D2 , , . , . ,

120 4

. Johnson & Johnson, 1994, Risperdal.

4.17 D2 ,

5-HT2A, 1 2, 1 . , , , , .

(lanzapine) ,

5-HT2 D2 . M3 , , 5-HT1, GABAA -. , Eli Lilly Zyprexa. Zyprexa 2008 4,7 $.

GPCRS A - GPCRs

, fight-or-flight. , - -. - : 1 2.

1 Gq , C (PLC), PIP2 IP3 (DAG). , 3 Ca2+. , 1- , , , . , , .

(phenylephrine) 1- , ,

121

, , , , , . 1- .

(xymetazoline) 1- 2-, . Merck 1961, . , .

4.18 ( Sudafed) ( 1- . (doxazosin) 1-,

Pfizer Cardura, . 1- (), .

(prazosin) 1-, Vasoflex, , . , .

2 (2A, 2, 2C), Gi , , cAMP. . . , , , .

(clonidine) 2-. 2 Ca2+ . . - 1950.

122 4

2010 (attention deficit hyperactivity disorder, ADHD). , ().

(yohimbine) Pausinystalia yohimbe (Yohimbe), . 2-, , . . , , , . , , . 2- , 1-20% 55 .

4.19 Pausinystalia yohimbe, 2-, , , . - 1, 2 3, Gs

, , cAMP. 1- , ( ), . 2 , , . 3 . - , 1962, Sir James W. Black - (beta

blocker

(chronic GlaxoSm

Ventoli

s),

c obstructiv mithKline in.

4.20 2-

20

(salmeter

ve pulmona

1980 (salbuta 2- .

- .

Nob

.

rol) ry disease, amol)

- James

bel 1988.

COPD). 19 (

(Serevent)

Black,

2 990 Sere ( 20

,

2- . event. 2- 0 min)

(Vent .

.

1.

olin),

1

. 1968

1962

123

124

1

4 19beta

Ten

4

4.22

4.21 962, blockers,

.

, , (normin, .

(atenolol)

(metopro (carvedilo

, ,

.

,

,

olol) ol)

(1, 2) .

.

beta b

-.

20

blocker,

, ,

1 block

1 . (

failure, C Coreg (G(Roche), 2007. ,

-

, ,

ker

1 blocker ,

1, 2) HF). GlaxoSmith Carlo

-.

Jame

(5

1 (congesti :

hKline), Doc (Cipla)

1 .

,

es Black,

1 2 , 5-1). .

1976 .

,

ive heart Carvil,

Dilatrend 2-

GPCR

4

4

Ther

.

RS

, GPCR , . ().

4.23

,

4.24 5 3 C rapeutic oppo

1-1

A

Rs.

.

.

Gq Ca2+, , portunities f

A

(

: / ,

2 4

from muscar

-

/

5

cAMP. rinic recepto

) ,

, ,

: 1, 2,

5 Gi R. Eglena,or research,

,

, 3, 4,

, C,

a, A. Choppin TiPS (2001)

5.

nb and N. Wa1) 22, 4094

1

: ,

1, 3

Watsonc, 414.

125

126 4

1 , , , . Gq , C 3 Ca2+. 1 AF102B, AF150(S) AF267B , , stress, tau, . Alzheimer .

2 , (sinoatrial node, SA) (atrioventricular node, AV), . 2 Gi , cAMP, - Ca2+ K+. , 2 , (), (AV node) .

4.25 2 , (SA) (AV). Gi + Ca2+. , (AV) .

2

Gi Gi

i i

127

M3 . Gq (PLC) Ca2+ . , 3 , , Ca2+ , . ( 3) . , 3 .

4.26 3 , , . M3 , . ,

, , .

(pilocarpine) 3 , 100 . , , , , . . , , 3 , Ca2+ . , , . , .

Muscarinic M3

128

4

Piloca

Sjgren

4

4.26

carpus microp

3 n.

4.27

. ophyllus,

,

3 Sjgr

3 (trabe .

ren,

,

ecular meshw

Salag

work), . .

gen Evo

,

Pil

(cilliar 3

xac,

locarpus mic

ry body) ,

(cevimelin

Venus Willi

crophyllus

ne), 3

iams.

129

4.28 Albert Ladenburg 1880 .

(- ) , Parkinson, , .

Parkinson , . . . Parkinson (benzatropine), Cogentin.

, , , Solanaceae , .

M1, M2, M3, M4 M5 , Atropa belladonna. "Essential Drugs List", . "belladonna" ( ) , , , . , .

2 : (SA) (AV). ( ), .

, . .

(scopolamine) , 1.

Solanaceae, . Brugmansia, , . , . , , , , , .

, . , 330 g ,

130

4

Bo

4

Boeh

4

4.29 Brugmans

. ehringer) . ,

4.29 ringer) -

,

, sia, Angel.

-

-

. Albe

l Trumpet

, -

,

ert Ladenbu

,

,

urg 1880

,

. , . .

,

.

Buscopan ( . .

,

Buscop

( ,

, pan ( -

,

48-

GPCR

, ,

, ,

4.30 .

RS

Na, , . ACE (ang 1 C Na+,

(ipratropiu (dime .

(d, .

A

: a+

,

. giotensin-co 1, 2, +

um) enhydrinate, , 8 , Dram

dimenhydrin, D

A

/

nverting en 3, 4. .

D

, A , ) 8- mamine

nate)

Dramamine

.

nzyme), G

, ,

iphenhydram

Atrovent, A , .

, ,

GPCRs

,

mine

Apovent, Ip ,

/ , 40 , .

G Ca2+ ,

8-chloro-t

praxa

.

: ,

, .

Gq +. , ,

theophylline

1

, , .

: ,

,

,

e

131

132 4

1 , (angiotensin receptor blockers, ARBs), - - . , , .

(losartan) T1 , 1995 Merck. . 1 , . .

4.30 , -, . (losartan) T1 , 1995 Merck.

133

GPCRS A

( 20- C). (COXs) (PGs) (TXs), (LTs).

4.31 ( ) ( 20 C), (COX1 COX2). E2, D2, F2a 2, 2, GPCRs, Gs cAMP ( EP1, EP2, EP3, EP4, DP1, DP2 ), Gq C (PLC) Ca2+ ( FP2 ).

,

,

PGE2 PGD2 PGI2 PGF2 Thromboxane A2

EP1, EP2, EP3, EP4 DP1, DP2 FP2 IP TP

2

Prostaglandin synthases

COX1

COX2

PLA2

134 4

, , . , , GPCRs, . , , sec min, .

, 1930 Raphael Kurzrok Charles Leib. PGE2 , .

(dinoprostone) 2, 1976 gel , Pfizer Inc Prostin E2, 2 . 17 , 25% .

(latanoprost) F2 Carl B. Camras Columbia University 1996. . Pfizer Xalatan, , . FP . FP (MMPs), (uveoscleral drainage). , . .

4.32 F2a. Xalatan , 1,6 $. FP (ciliary body) , (uveoscleral pathway). , , (trabecular pathway) .

135

- . Bengt Samuelsson 1979, , . 5-- (, , , ). shock. Ca2+, 5-- 2 (LTA2). LTB4, , LTC4, , LTD4 LTE4. -.

4.33 .

Ca2+ 2 (PL2). 5-- LTA2. LTB4, , LTC4. LTC4 - LTD4 LTE4. LTC4. LTB4 , LTD4 LTE4 . LTB4

, . LTC4 LTD4 SRSA, . , ontelukast afirlukast, , , . montelukast D4

136 4

-, CysLT1, , .

GPCRS A (ADH: antidiuretic hormone:)

, : / H2, H2 , , / .

4.34 (osmolarity) (ADH) . ADH , Henle , , , . , Henle , .

3 GPCRs: V1, V2 V3. V1a , ,

. Gaq, C, IP3 Ca2+, .

V1b V3 , Gaq C, ACTH.

V2 , ( Henle ),

:

(ADH)

2

137

. H2O .

,

(desmopressin) .

V2 von Willebrand . DesmoMelt, Stimate, Minirin, , (diabetes insipidus)2, , ( von Willebrand ).

, , V1a V1b ACTH, . , 10 , 1500 . , (. Na+). a+ (), , , , . .

, (terlipressin) V1 . Teripress Glypressin , shock.

2 ( "" ) (), . V2 , .

2.

.

138 4

, , .

4.35 , ,

V2 GPCRs , , H2. , , V1 GPCRs , C . J. Finley, M. Konstam, J. Udelson, Arginine Vasopressin Antagonists for the Treatment of Heart Failure and Hyponatremia, Circulation 118: 410-421 (2008).

ADH

ADH

139

4.36

V2 , , .

(VRAs, Vasopressin receptor antagonists) , (vaptan drugs), 2009. (SIADH, syndrome of inappropriate antidiuretic hormone secretion), . , , , . SIADH, , , , .

(tolvaptan) V2, Otsuka Pharmaceutical Co, 2009. Resodim Na+.

GPCRS A

, Papaver somniferum Sertrner, 1803. 1827 Merck, Darmstadt, . , , , , , . GPCRs . , (1, 2, 3) , (1, 2), (1, 2, 3) , .

, , , .

140 4

1 , 2 , .

.

. ( ), , , . () , , .

, , , . .

:

(fentanyl). , . , , , . , , . .

4.37 GPCRs . , Gi . cAMP Ca2+ . , + + . .

141

, , , . . 1832 Pierre Robiquet.

: , , , .

: , (naloxone) , , 17 . . . , . 1-3 , , . 1960 Sankyo Narcan.

4.38 , 17 . .

GPCRS A TH GnRH (GONADOTROPIN RELEASING HORMONE) GnRH, ,

. - , GPCRs , GnRHRs, . GnRH , Gq PLC, 3 Ca2+. PKC, : (LH) (FSH) . , , .

17

142 4

4.39 GnRH ,

, GPCRs , LH FSH, , .

4.40 GnRH , Gaq

PLC. PKC, (LH, FSH).

GnRH.

GnRH , , ( ).

GnRH , , LH FSH.

LH FSH .

143

GnRH , , GnRH, , down regulation , , LH FSH, , . .

GnRH . 8-14 , 9-14 . , , 35-70 . GnRH - : . ,

. , .

transsexual , trans women.

in vitro fertilisation (IVF), FSH. GnRH, -, FSH , (hCG), 3.

, .

GnRH GnRH, 6 10. . FSH LH. , 10 , FSH LH, down-regulation .

700 GnRH: leuprolide (Lupron, Eligard), buserelin (Suprefact, Suprecor), histrelin (Supprelin, Vantas), goserelin (Zoladex), and deslorelin

(Suprelorin, Ovuplant).

4.41 leucopride (Lupron) GnRH . , GnRH, , . in vitro (IVF).

3 , LH FSH .

, . , GnRH LH FSH. , GnRH . GnRH .

144 4

GnRH GnRH, . GnRH GnRH , LH FSH. LH , . GnRH, --, , , .

, (castration) . GnRH GnRH.

GnRH LH FSH in-vitro (IVF). hCG - . GnRH, Cetrorelix Ganirelix

Cetrorelix GnRH. - (, ). , cetrorelix , GnRH , LH FSH. . LH hCG

.

4.42 To cetrorelix (Cetrotide) Serono LH FSH in-vitro (IVF).

G

likerecrecepto

VPAC1, Gs

G

Ca2+,T1

GPCRs

1,(),(GHRH),

2ceptors(EMRors

() ,

GPCRs

CCC

1

,PACAP(pi

R),leukocyte

vasoact VPAC2 ,

,

, )

ituitaryaden

EGFecellsurface

tive intestin , (

, VIP.

C

(GAB

, , . .

nylatecyclas

NHeantigenCD9

nal peptide , ). P.

GPCRs BAB), GABA2.

,

,

(((111555)))

27141((CRH),eactivating

H2:EG97,calciumin

(VIP) , c

VPA

, , >27,

(15):VIP),popypeptide

Fmodulecondependent

, , cAMP,

AC1 VP

C (mGlu2/

GA

(

, , 7 /

e)

ontainingmulatrotoxin

PAC2

/3) G

(((222222)))

ABAB,

1

20 ,

,

ucin

: - ,

GABA GABA1 . G-.

145

146 4

2. (Ligand-gated ion channel receptors) - - .

2 : cys-loop , 5 (2) ( , GABAA GABAC, 5-3), , 4 ( NMDA, AMPA ).

4.43 - GABAA. 5

(2) (), , .

- ,

, : a+ Ca2+ , 5-3 , Cl- GABAA, GABAC . (depolarization) -. , 5-3 ( NMDA, AMPA ), . (hyperpolarization) -. GABA, GABAC .

, msec, (fast responding receptors), G, , G, (effector) . -

O (subunits) - (4 5) : 4 , - - , - .

147

4 EN (-V). 20-30 -, . ( 20) .

4.44 5 2 GABAA. 4 (1, 2, 3, 4). G.B. Smith and R.W. Olsen, TiPS 1995, 16, 162-167.

( , ) ( 5,6 ). , . (Pro) .

, (Ser248, Ser254, Ser256, Ser262) , (non competitive blockers)* ( 3.14). (. , , ) (), , -.

* , . (D). . . J-P. Changeux et al, Achetylcholine receptor: an allosteric protein, Science, 1984, 225, 1335-1344.

148 4

4.45 . -. 4 (1-4), 20-

30 - . . . 2 . H.R. Arias, Brain Res.Rev., 1997, 25, 133-191. 4.46 , 2 Ch . CPZ (), (-), TID Arias H.R., Brain Res. Rv., 1997, 25, 133-91.

4.47 .

-. (high affinity site) . 30 , (low affinity sites) . J-P. Changeux et al, Science, 1984, 225, 1335-1343. 1 E 2 ,

.

A B

149

: GABAA, Cl-, , Na+ +. - , (driving force) .

- , cAMP. .

4.48

. Hucho F. et al, TiBS, 1994, 19, 383-387.

AMINOTEIKO AO (NH2-TERMINAL). , . (2) GABA 5-3, -, . . , .

- GABA . GABA . GABA .

(Cys139 Cys153), S-S. Cys-Cys , .

, . . , , , ( - -). (2).

150 4

(COOH-TERMINAL). G, , - .

4.49 . Cys138- Cys152 Cys198-Cys209, . Laube B. et al, TiPS, 2002, 23, 519-527.

. , . , . , . . 2-3 nm . . 2 . - .

4.50 () , . ,

. . . () 2 . Unwin N., Achetylcholin receptor channel imaged in the open state, Nature, 1995, 373, 37-43.

.

151

. . , 2 . . . . , . , 2. 2 . . 2 , . .

4.51 () 2 . ( ) . . () 2 . 2 . (): 2 . . (): 2 . 2 . ( ) , . Unwin N., Achetylcholin receptor channel imaged in the open state, Nature, 1995, 373, 37-43.

prefilter

M2M2M2

152 4

- - . , , NMDA (--D-), AMPA (--3--5--4- ) . NMDA , . , NMDA . NMDA LTP ( ). , Ca2+. NMDA . NMDA :

.

AMPA NMDA. NMDA Mg2+ ( Zn2+),

. , Na+.

Mg2+ NMDA.

NMDA a+ Ca2+.

4.52 NMDA, ,

. NMDA ( Mg2+ ) ( Na+). , Mg2+ NMDA a+ Ca2+.

153

NMDA

NMDA -, NR1 2 NR2A, NR2B, NR2C NR2D ( NR1-NR1-NR2A-NR2A). 3 (1, 3 4). 2 . 2 2 . 2 , , S1, S2, COO- , .

2 . 2 -, 1 3 . Q/R/N . (Q), (R) , () DA.

4.53 NMDA. (NR1-NR4). 3 (1, 3

4). 2 2 . NMDA, -, . NMDA PCP (phencyclidine, ) (angel dust) . 4.54 NMDA.

154 4

3. (Receptors tyrosine kinase)

. .

. , . , .

: (EGF: epidermal growth factor), (PDGF: platelet-derived growth factor), (NGF: nerve growth factor), . (growth factor receptors). .

- : ( EGF, NGF, PDGF) ( ). /

, . ( ) , ( ) . , , . H EGF. , . EGF , .

4.55 (EGF) ,

, . (Protein Tyrosine Kinase) , . . J. Schlessinger, TiBS, 1993, 18, 273-275.

155

H PDGF. 5 ( ) (immunoglobulin-like domains). , (kinase insert region). , -.

4.56 PDGF ( ). . . - , -, GAP (GTPase activating protein), 3- C- (PLC-). 85 / - -. W.J. Fantl et al, Annu. Rev. Biochem., 1993, 62, 453-481.

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