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1. MAP s

2.

GPCRs

3. ERK

4. JNKASK1/JNK

JNK Wnt

(Scaffold proteins) JNKJNK

5. S. cereviciaeFus3 ss1

6.

11

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350

1.

,

. ,

(cAMP, DAG, IP3), (PKA, PKC, CAM-kinase) .

,

, , .

,

, .

(:

), mitogenic

activated protein kinases cascade MAPK cascade.

, . MAPKs

: , , stress .

s

MAPKs ,

. s

s, s.

(MAPK)

(MAPKK)

(MAPKKK)

,

(scaffold proteins). s

S. Cerevisiae, Ste5 Pbs2p. s : 1)

5/28/2018 11.

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351

2)

.

11.1MAP .

. , (scaffold proteins).. JIP-1 JNK.

MAPKs,

.

3 MAPKs ,

,

-:

1. :RafMEK1-2 ERK1-2 (Extracellular signal-Regulated Kinase).

2. (TNF-, UV, ): 1-5, 1, SK1 4,7 JNK (Jun NH2-

terminal Kinase)SAPK (stress activated protein kinase).

3. (TNF-, UV, 22): MEKK4, 1, ASK1 3,4,6p38/HOG.

.

.

5/28/2018 11.

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352

ERK JNK/SAPK p38/HOG

TNF-, UV, ILs, stress TNF-, UV, H2O2,

stress

GEF Grb2/hSos - -

GTP-binding protein Ras Rac/Cdc42 -

Raf

MEK1-2

ERK1-2

MEKK1-5, TAK1, ASK1

MEK4,7

JNK SAPKs

MEKK4, TAK1, ASK1

MEK3,4,6

p38/HOG

p62TCF c-Jun, p62TCF, ATF2 c-Jun, CREB, ATF2

11.2 s.

RKs (Extracellularsignal-Regulated Kinases). Ras (

-Ras).

- H Ras ( Raf). Ser/Thr, ,

Ser, (MEK: MAP/ERK Kinase).

- () Thr Tyr,

5/28/2018 11.

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353

-hrXTyr-. MARKK

,

Ser/Thr Tyr.

, (RKs).

- () -hrXTyr-, .

,

.

ERK: Extracellular Regulated

MEK: MAP/ERK Kinase

MEKK: MEK Kinase

11.3ERKs.Ras. H

Ras , Raf MEKK-1.

(). ,

, (

RK1-2). ERK

.

2.

(RTKs),

G (GPCRs) G

G .

-Tyr

, PDGF (platelet derived growth factor)

EGF (epidermical growth factor)

(RTKs),

Tyr. Tyr

5/28/2018 11.

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354

SH2 , Grb2

(growth factor receptor binding protein). Grb2 SOS,

, GTP

Ras.GDP, GDP GTP. Ras C-

. Ras.GTP

, Ser/ThrRaf, MAP kinase kinase kinase (MAPKKK).

Raf

, Ser 14-3-3.

Ras,

.

( 2),

Raf,

Raf Ras.

, , ,

KSR,

14-3-3 . 2,

KSR, ERK

. KSR , Raf,

. , Raf KSR-MEK-ERK

(KSR/ Raf-MEK-ERK)

.

11.4 . Raf

KSR , 14-3-3,

[1].

, Ras

(Ras.GTP)

Raf KSR

,

Ras [2]. Anderson D., Role of

lipids in the MAPK signalling pathway, Progress in Lipid

Res. 2006, 45, 102-119.

.Raf. -CR1, Ras-binding domain

(RBD) cysteine-rich domain (CRD). CR2

Ser/Thr,

(D) C-CR3.

a.

[1]

[2]

. Raf

5/28/2018 11.

7/38

356

s

. , RTKs PLC (

9). DAG Ca2+ PKC.

PKC Raf-1 ()

JNK (),

.

11.7 . RTK Ras, Raf. , Raf

MEK/ERK. Tyr

PLC,

PKC. PKC Raf

.

GPCRs

GPCRs

, ,

GPCRs .GPCRs MAPKs.

, , RTKs,

,

, GPCRs MAPKs RTs.

GPCRs, 1, -1,

, , (LPA), -,

(mACh), , 2 ,

PKs,

. GPCRs s

, G .

RTK

/R

Protein Kinase C

-TyrPO4 PLC

RTK

5/28/2018 11.

8/38

357

GPCRs

Ks, ,

( COS-7, HEK-293 )

MAPK GPCR . ,

GPCR MAP .:

o (PTX), GiGq, G

.G

G.

o . 3-, GPCR , PI3.

o . 3-, GPCR -,

PI3.

o . 3-, GPCR ,

PI3.

GPCRs MAPKs.

1. trans-RTKs2. 3. PKC

PKs .

12 MAPKs, 7 MAPKKs 14 MAPKKKs, .

G MAPKs

, GPCR

G ,

G

G .

G :

Gs, Gq, Gi, G12. K

.

Gas

, s

,

5/28/2018 11.

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358

c

cAMP , Ras-GEF (RAS-guanine nucleotide exchange factor), Epac (exchange protein directly

activated by cAMP).

GRap1,

/ERK. , B-Raf, Rap1 B-Raf,

RK, , , ,

Raf1, Rap1 Raf1,

ERK.

/ -Raf

Raf-1

11.8B-Raf, Rap1 B-Raf, RK, , ,

Raf1, Rap1 Raf1,

ERK. Stork P., Schmitt J., Crosstalk between cAMP and MAP kinase signaling in the

regulation of cell proliferation, Trends in Cell Biology, 2002, 12, 258-266.

, Raf1 : Src, GTP

Rap1, Raf1,

Akt, Raf1 Ser ,

Raf1 Ser,

.

5/28/2018 11.

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5/28/2018 11.

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359

11.9 H Src, GTPRap1, Raf1, Raf1

Ser., Raf1 Akt. Stork P., Schmitt J., Crosstalk between cAMP and MAP kinase signaling in the

regulation of cell proliferation, Trends in Cell Biology, 2002, 12, 258-266.

Gi

s, i cAMP. -

i (gip2) ,

GPCRs Gi s.

Gi-coupled receptors s

G, 3-, Src,

EGF (EGFR).

, trans-

EGFR

. ,

i ,

Rap-GAP,

Rap1 ( GTP),

,

-Raf (

KK)

Raf-1 ( KK),

.

ShcShc

5/28/2018 11.

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360

Gq Gq

Ks.

H Gq C (PLC),

- (2) : DAG () IP3

(). 3Ca2+, : CaM kinase II, Ras-GAP (Ras-GTPase-

activating protein) Ras

Raf/MEK/ERK.

C (PKC) ,

DAG.

PKC Raf,

Ras.

C 2(, ). 2 trans-

, Grb-Sos-Ras

Raf/MEK/ERK. C , Src.

Src , Shc, trans- RTK,

Grb-Sos-RasRaf/MEK/ERK

C, ,

, BTK (Bruton tyrosine kinase),

. ,

ERK ,

JNK.

Gq, PLC.

Ras-GAP

PLCPLCGPCRaq

PKC

Raf

MEK

ERK

Shc

Grb

Raf

MEK

ERK

CAM

BTKBTK

PYK2PYK2

IP3/Ca2+

DAG

RasRasSos

SrcSrc

Ras

5/28/2018 11.

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361

G12

,

12Ras-GAP. 12 (pleckstrin

homology) . , 100

, ,

, -

.

p120 Ras-GAP

11.10 p120 Ras-GAP. G12.

, MAPKs

trans-R, Grb-Ss-Ras .

12 Ras-GAP Ras-GAP,

Ras ERK.

, G12

Rho. 12 Rho, Rho-GEF, PTKs, Rho-GEF.

G

G MAPKs

GPCRs, . -

3-.3-:

(. Src), trans- RTKs. RTKs

Grb-Sos-Ras s.

Vav (Rac-GEF), GTPRac. , Rac

JNK.

Ras-GEF (Ras-guanine-specific nucleotide-exchange factor),

Ras MAPKs.

Pro-Pro-Pro SH3 SH2 Kinase

12

SH3SH2 Ras-GAP domain

12

SH2

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362

11.11 , Raf/MEK/ERK.

:

1. RTK, Shc/Sos/Grb2 Ras, Raf//ERK.

2. GPCR, Gs/cAMP/PKA EpaC Rap, Raf Raf-1

Gaq/PLC/PKC Raf-1,

Gaq/PLC/2 tras- RTK

G/ 3 / Src tras- RTK

-/ Src tras- RTK.

.

Marinissen M., Gutkind S., G-protein coupled receptors and signaling networks: emerging

paradigms, Trends in Pharmacol. Sci., 2001, 22, 368-376.

MAPKs GPCRs, G-

GPCRs MAPKs,

G .

1. trans-RTKs GPCRs RTKs GPCRs

.

, proheparin-binding EGF (pro-HB-EGF),

-GF. , -EGF -

GFR, o MAPKs.

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363

HB-EGF

Pro-HB-EGF

Shc

2. -MAPKsGPCRs , .

GPCR- (GRKs)

, , -, AP2 (adaptor

protein-2) . -

G-

.

11.12 (), GPCR G . ()GRKs, -GPCR. ()-GPCR . Lefkowitz R., Whalen E., -

arrestins: traffic cops of cell signaling, Current Opin. Cell Biol. 2004, 16, 162-1168 .

, GPCRs,

-. -COS-,

5/28/2018 11.

16/38

364

s -.

-:

1. Src,

, : ) ,

, ) Ras/ Raf-

MEK-ERK1/2, ) -8.

11.13- Src GPCRs.

: 1)

, 2) Ras ERK1/23) . M. Luttrell and J. Lefkowitz, The role

of b-arrestins in the termination and transduction of G-protein-coupled receptor signals, Journal of

Cell Science 115, 455-465, 2002.

2.-GPCRs,

, -.GPCR / -/ Raf-MEK-ERK

RK . ERK1/2 -

RK1/2.

, ERK -

,

5/28/2018 11.

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365

DNA .

11.14-. GPCR , -,

(GPCR/-/Raf-MEK-ERK)

. , ERK , () . M.

Luttrell and J. Lefkowitz, The role of -arrestins in the termination and transduction of G-protein-

coupled receptor signals, Journal of Cell Science 115, 455-465, 2002.

, ,

-,

.

Raf-MEK-ERK, - KSR

, - .

-, 1 (MEK partner 1),

p14, ERK (Raf) .

,

.

11.15

(KSR),

(-)

(1). Anderson D.,Role of lipids in the MAPK signalling pathway,

Progress in Lipid Res. 2006, 45, 102-119.

5/28/2018 11.

18/38

366

3. ERK

1.ERK .

ERK . ,

,

(early response genes). EGF PDGF, .

c-fos, c-myc

c-jun,

.

c-fos, SRE (serum response element),

p62TCF p62SRF

. ERK p62TCF

p62TCFp62SRFSRE, c-fos.

, c-Fos c-Jun,

(-1, activator protein complex), .

(1)

ERK

11.16 (c-fos) RK. EGF

GTPRas. (ERK) ,

p62TCF

. O p62TCF

, p62SRF

,

c-fos, .

Gomberts B., Kramer I., Tatham P., Signal Transduction, Elsevier, 2002.

5/28/2018 11.

19/38

367

2.ERK .

mRNA. ERK

.

5 mRNA,

40S, mRNA, , eIF-4E. eIF-4E

mRNA

eIF-4G, eIF-4A eIF-4, mRNA 40S

. ERK eIF-4E,

, MNK-1 (MAP kinase integrating kinase-1),

ERK, eIF-4E,

mRNA.

ERK:

11.17 RK. ERK -1,

eIF-4E.

(eIF-4G, eIF-4A, eIF-4B) -mRNA,

mRNA 40S .

Gomberts B., Kramer I., Tatham P., Signal Transduction, Elsevier, 2002.

3. ERK .ERK

, , , .

,

HGF (hepatocyte growth factor) c-Met Raf-1. ERK

5/28/2018 11.

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368

yr118 Src. ERK

Ser83,

FAK (focal adhesion kinase). FAK :

3- GTP Rho , Rac,

, FAK

, .

11.18 ERK FAK. . ,

HGF c-Met Src Raf

ERK. ,

. Kolch W., Coordinating ERK/MAPK

signaling through scaffolds and inhibitors, Nature Reviews, Mol. Cell Biol., 2005, 6, 827-838.

4.ERK. ,

ERK, -1, ERK . .

-1 (kinase phosphatase-1) ,

11.19 ERK , ,

MKP-1, ERK.. Gomberts B., Kramer I., Tatham P., Signal Transduction, Elsevier, 2002.

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369

4. JNK

JNK (c-Jun NH2 terminal kinase, 2-

c-Jun) stress, , - ( -1 TNF-

tumor necrosis factor), stress (, , pH), Ca2+, SAPK (stress-activated

protein kinase).

stress [1-5, -1 (TGF- activating kinase),

ASK-1 (apoptosis signal-regulatory kinase)],

(4,7), JNK1-3 (. 11.20).

, JNK

c-Jun (). c-Jun c-Fos

Ap-1 (Activator protein 1). Ap-1

, ,

, . c-Jun,

JNK, (F2, p53 ). JNK

(16, ), JNK

.

-PO4-PO4 AP-1

11.20stress (TNF) JNK. JNK c-Jun -1. -1 (c-Jun + c-Fos) DNA (TRE)

, ,

.

ASK1/JNK

JNK

ASK1(apoptosis signal-regulating kinase 1). ASK1

Ser/Thre, ,

2

2,

GPCRs,

Ca2+. ,

Stress/(TNF)

1-5, 1, SK1 ()

4,7 ()

JNK1-3 ()

c-Jun

c-Fos

TRE: TPA Responsive Element (DNA binding element)

5/28/2018 11.

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370

ASK1 4/7 3/6,

JNK .

SK1 , C-

coiled-coil . ,

, , 14-3-3

rx, . ASK1, ,

Thr (Thr845 , Thr838 )

.

11.21 ASK1. Matsukawa J., Takeda K.,Ichijo H., The ASK1-MAP kinase cascades in mammalian stress response, J. Biochem., 2004, 136,

261-265.

ASK1. ROS

(reactive oxygen species) ( 22)

, ,

.

22 Trx, ASK1 . ROS

ASK1/JNK: TNF (tumor necrosis

factor) TRAF2 (TNF receptor associated factor 2)

GPCR .

, TNF,

.

ASK1.ASK1/JNK

.

Ser/Thr , IRE1, ASK1, TRAF2.

, Huntington ,

huntingtin Q .

ASK1/JNK .

Ca2+ASK1.Ca2+

Ca2+-RK

. -

I(CaMKI) ASK1/p38,

.

ASK1. Fas,

SK1

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371

FasL : FADD

8, Daxx, -

ASK1 JNK (16, ).

11.22ASK1 .ASK1 Trx,

. ROS F

GPCR, Trx, ASK1

. ASK1 Ca2+

,

CaMKII,

. ASK1

JNK . Matsukawa J., Takeda K., Ichijo H., The ASK1-MAP

kinase cascades in mammalian stress response, J. Biochem., 2004, 136, 261-265.

GPCR JNK.

JNK GPCRs.

G13

JNK, , ASK1, 4/7,

JNK. , GPCRs Gq G13

JNK Rac/Cdc42

(. 11.23).

5/28/2018 11.

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372

11.23GPCRs JNK. GPCRs GqG13JNK Rac/Cdc42

. G13JNK,

, ASK1, 4/7,

JNK.

JNK Wnt

Wnt/Wingless

, ,

.

. ,

Wnt .

Wnt Wnt

Frizzled (11.24). Wnt,

Frizzled : Wnt JNK. ,

Dishevelled.

Wnt, Dishevelled

GSK3, -, Axin, APC (adenomatous polyposis coli).

-,

TCF, , c-myc

cyclin-D1. , Dishevelled GTP

Ras, Rho, JNK,

.

Wnt

. PAR-1 Naked.

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373

11.24 () -() Wnt.

Frizzled (Fz)

Dishevelled (Dsh),

3 (DIX,

PDZ, DEP). DIX PDZ

Dsh,

Wnt DEP

Wnt (JNK).

Dsh,

.

PAR-1 Naked,

Wnt,

JNK. Weston & Davis, Current

Opinion in Genetics & Development

2002, 12: 14-21.

PAR1: Dishevelled - PDZ . Wnt

PAR1 Wnt

upstream -Axin.

PAR1 JNK Dishevelled,

.

Naked: Wnt/ - JNK. naked

downstream Wnt-1 upstream -

PDZ Dishevelled.

(Scaffold proteins) JNK

( )

JNK.

,

JNK Crk II, , -

JIP:

Crk II (adaptor protein): - SH-3 Crk II

- JNK.

JNK Rac1 (G-

).

() ()

5/28/2018 11.

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374

(280):, . MKK4,

MKK7 JNK.

-: --1 -2. --2

JNK, ASK1, MKK4 JNK3.JIP: JIP MLKs (mixed-lineage protein kinases)

MKK7 (11.19). JIP JIP1

JIP2 ( 1 2 ). JIP

. ,

JIP1 -,

.

JNK,

.

JNK

JNK (Jnk1, Jnk2, Jnk3). Jnk1Jnk2

, Jnk3 .

knockout Jnk1, Jnk2Jnk3(

) ,

.

Jnk1Jnk2,

.

11.26

(exencephaly),

,

.

11.25 H JIP-1 (scaffold protein) JNK.

JIP-1 MLK7,

JNK.

www.le.ac.uk/bioche/research/md38_r.html.

5/28/2018 11.

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375

- 4, 7,

.

, JNK .

4 7 JNK.

stress, 4 7

JNK Tyr Thr , JNK.

- knock out ,

JNK. ,

(MEKK1-4) JN.

MEKK1 ,

,

JNK, MEKK3 .

: JN, , , .

JNK .

JNK. (CrkII, , --2,

JIP2 JIP3) MAPKKK JNK (MLK, ASK2,

MEKK2, MEKK4 TAK1). ,

.

JNK

.

5. S. cereviciae

, .

,

.

,

,

, ,

, .

s (mitogen activated protein kinases)

. , 5

s

(mating), (invasive

growth), o,

, .

5/28/2018 11.

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376

11.27

.1. Fus3 .

2. Kss1, .

3. Hog1, .

4. shock Mpk1,

.

5. C N Smk1, .

5/28/2018 11.

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377

.

, Saccharomyces cerevisiae

. ,

a .

(

): , a , a a

.

, ,

(Ste11/Ste7/Fus3).

GPCR

G-,

Ste5 . , ,

Ste20, Ste11 (MAPKKK),

Ste7 (MAPKK),

MAPKs Fus3Kss1. Fus3 Kss1

Ste12, (11.28). s Far1,

.

11.28 (a mating factor) S. cerevisiae.GPCR G . G

Bem1, GAP , G (Cdc42 Cdc24),

Rho

, (morphogenesis)

. , (Ste11,

Ste7, Fus3/Kss1), Far1

Fus3 , , Ste12 .

5/28/2018 11.

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378

11.29 Saccharomyces cerevisiae., .

a .

:

, a , a a

.

. ,

, .

a

a

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379

STRESS .,

,

stress:

(pseudohyphal growth) ,

(invasive growth) , .

, Ste20, Ste7, Ste12 Ste11,

Ste5, . ,

, MAPK

, , ,

.

, mating/filamentous

.

11.30 (sexual conjugation/invasive growth/filamentous growth)MAPK .,

. ,

(invasive growth). , , .

Ashton Breikreutz and Mike Tyers, MAPK signaling specificity: it takes two to tango, Trends in

Cell Biology, 2002.

Low nutrient

5/28/2018 11.

32/38

380

11.31 Saccharomyces cerevisiae. (Yeast-forming growth). H

(pseudohyphal growth) ,

,

(hyphal growth). Graeme M. Walker, Yeast, Physiology and Biotechnology, 2000.

11.32 H. www.Yeastgenome Org/yeast-

images.shtml.

Fus3 Kss1

(mating)

.

s (Fus3 Kss1). , s

.

. Fus3

Ste5, Kss1

, .

Fus3 ,

Kss1 , Far1,

Fus3. Far1

5/28/2018 11.

33/38

381

. , Fus3

.

Fus3 Kss1 , , Kss1

,

Fus3, .

, mating/filamentous , .

Fus3 Kss1.

.

, Fus3 Ste5,

Kss1 . ,

Fus3 Far1, Kss1, in vivo

in vitro. , Kss1

Fus3.

11.1

s -, .

Garington T. and Johnson G., Organization and regulation of mitogen-activated protein

kinase signaling pathways, Current Opinion in Cell Biology 1999, 11, 211-218.

5/28/2018 11.

34/38

382

6. s

,

, ,

. , MAP

. , , ,

, , . s

, ,

.

Arabidopsis

thaliana 60 s, 10

s 20 s.

11.33 s . . ,

Arabidopsis, (alfalfa) , , (

), stress, , s.

Tena G., Asai T., Chui W., Sheen J., Plant mitogen activated signaling cascades, Curr. Opin. Plant

Biol., 2001, 4, 392-400.

. ( , , ).

5/28/2018 11.

35/38

383

() ,

, ,

.

s.

, .

,

.

.

.

stress.

.

. ,

. -

AtHK1 (Arabidopsis thalianaHistidine Kinase 1),

(AtMEKK1-AtMKK1/2-AtMPK4).

,

.

, ROS,

.

.

. Arabidopsis,

(flg22) FLS2 MEKK1-MKK4/5-

MPK3/6 .

,

,

- . -

-

.

. NtNPK1-

NtMEK1-Ntf6. 1 ,

NACK1 (NPK1-activating kinase like protein1)

, .

NACK1 1 .

G2, 1

, CK1/2 . CK1

- (CDK) , 1. , CDK

1. NACK1/2

5/28/2018 11.

36/38

384

1 .

, CDK 1

NACK1.

. 1 .

G1, NACK1 1 .

11.3 4 1, . 1G2 , .

(), 1

NACK1. CDK

. CDK , 1

, NACK1 . Jonak C., Okresz L.,

Borge L., Hirt H., Complexity, cross talk ant integration of MAP kinase signaling, Current Opinion in

Plant Biology 2002, 5, 415-424.

Anderson D., Role of lipids in the MAPK signalling pathway,Progress in Lipid Res. 2006,

45, 102-119.

Breikreutz Ashton and Mike Tyers, MAPK signaling specificity: it takes two to tango, Trends

in Cell Biology, 2002, 12, 254-257.

Garington T. and Johnson G., Organization and regulation of mitogen-activated protein kinasesignaling pathways, Current Opinion in Cell Biology 1999, 11, 211-218.

Graeme M. Walker, Yeast, Physiology and Biotechnology, 2000.

Jonak C., Okresz L., Borge L., Hirt H., Complexity, cross talk ant integration of MAP kinase

signaling, Current Opinion in Plant Biology2002, 5, 415-424.

Kolch W., Coordinating ERK/MAPK signaling though scaffolds and inhibitors,Nature

Reviews, Mol. Cell Biol.,2005, 6, 827-838.

Kraus S., Naor Z., Seger R., Intracellular signaling pathways mediated by the GnRH receptor,

Arch. Med. Res.,2001, 32, 499-509.

Lefkowitz R., Whalen E., -arrestins: traffic cops of cell signaling, Current Opin. Cell Biol.

2004, 16, 162-1168.

Lefkowitz R., Shenoy S., Transduction of Receptor Signals by -arrestins, Science2005, 308,512-517.

5/28/2018 11.

37/38

385

Liebmann C., Regulation of MAP kinase by peptide receptors signaling pathway: Paradigms

of multiplicity, Cellular Signalling, 2001, 13, 777-785.

Lowes V., Ip N., Wong Y., Integration of signals from receptor tyrosine kinases and G-

protein-coupled receptors,Neurosignals, 2002, 11, 5-19.

Luttrell LM and Robert J. Lefkowitz, The role of -arrestins in the termination and

transduction of G-protein-coupled receptor signals,Journal of Cell Science 2002, 115,455-465.

Matsukawa J., Takeda K., Ichijo H., The ASK1-MAP kinase cascades in mammalian stress

response,J. Biochem.,2004, 136, 261-265.

Naor Z., Benard O., Seger R., Activation of MAPK cascades by G-protein-coupled receptors:

the case of GnRH receptor, TEM, 2000, 11, 91-99.

Park HS, Huh SH, Seo JS, Choi EJ Hsp72 functions as a natural inhibitory protein of c-jun

N-terminal kinase.EMBO J.2001, 20:446-456.

Putcha GV, Moulder KL, Golden JP Induction of BIM, a proapoptotic BH3-only BCL-2

family member, is critical for neuronal apoptosis.Neuron2001, 29: 615-628.

Rincon M, Davis RJ, Flavell RA Signal transduction by MAP kinases in T lymphocytes.

Oncogene2001, 20, 2490-2497.Shenoy S., Lefkowitz R., Multifaceted roles of -arrestins in the regulation of seven-

membrane-spanning receptor trafficking and signaling, Biochem. J., 2003, 375, 503-

515.

Stork P., Schmitt J., Crosstalk between cAMP and MAP kinase signaling in the regulation of

cell proliferation, Trends in Cell Biology, 2002, 12, 258-266.

Tena G., Asai T., Chiu W, Sheen J., Plant mitogen-activated protein kinase cascades, Current

Opinion in Plant Biology2001, 4, 392-400.

Weston C.R., & Roger J Davis. The JNK signal transduction pathway. Current Opinion in

Genetics & Development2002, 12, 14-21.

Whitfield J, Neame SL, Paquet L,Ham J. Dominant negative c Jun promotes neuronal

survival by reducing BIM expression and inhibiting mitohondial cytocrome c release.

Neuron2001, 29, 629-643.

Wulf GM, Ryo A, Wulf GG, Lee SW Pin1 is overexpressed in breast cancer and cooperates

with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin

D1.EMBO J2001, 20, 3459-3472.

Yamamoto T, Ogawa S, Hirai H, Nishida E. The evi-1 oncoprotein inhibits c-jun N-terminal

kinase and prevents stress-induced cell death. EMBO J2000, 19, 2958-2968.

5/28/2018 11.

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