Hücrede Sinyal İletimiHücrede Sinyal İletimi

Nefize Ezgi Altınışık2601110400

ÇeşitleriÇeşitleri

• Temas bağımlı sinyal iletimi• Parakrin sinyal iletimi• Sinaptik Sinyal iletimi• Endokrin sinyal iletimi

Salgı Sinyalleri

(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.

(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

Local regulator diffuses through extracellular fluid

Target cell

Secretoryvesicle

Electrical signalalong nerve celltriggers release ofneurotransmitter

Neurotransmitter diffuses across

synapse

Target cellis stimulated

Local signaling

Figure 11.4 A B

Hormone travelsin bloodstreamto target cells

(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

Long-distance signaling

Bloodvessel

Targetcell

Endocrine cell

Figure 11.4 C

EXTRACELLULARFLUID

Receptor

Signal molecule

Relay molecules in a signal transduction pathway

Plasma membraneCYTOPLASM

Activationof cellularresponse

Figure 11.5

Reception1 Transduction2 Response3

YanıtlarYanıtlar

• Hayatta kalma• Büyüme ve Bölünme• Farklılaşma• Ölüm

Yanıtlar hızlı ya da yavaş olabilir.

Cross-talk (Çapraz Cross-talk (Çapraz Yanıt)Yanıt)

Response 1

Response 4 Response 5

Response

2

Response

3

Signalmolecule

Cell A. Pathway leads to a single response

Cell B. Pathway branches, leading to two responses

Cell C. Cross-talk occurs between two pathways

Cell D. Different receptorleads to a different response

Activationor inhibition

Receptor

Relaymolecules

Figure 11.15

ReseptörleReseptörlerr

G-protein-linkedReceptor

Plasma Membrane

EnzymeG-protein(inactive)CYTOPLASM

Cellular response

Activatedenzyme

ActivatedReceptor

Signal molecule Inctivateenzyme

Segment thatinteracts withG proteins

GDP

GDP

GTP

GTP

P i

Signal-binding site

Figure 11.7

GDP

G Proteini Bağlı Reseptörler

ReseptörlerReseptörlerSignalmolecule

Signal-binding sitea

CYTOPLASM

Tyrosines

Signal moleculeHelix in the

Membrane

Tyr

TyrTyr

TyrTyr

TyrTyr

TyrTyr

TyrTyr

Tyr

Tyr

TyrTyr

TyrTyr

Tyr Tyr

TyrTyr

TyrTyr

Tyr

Tyr

TyrTyr

TyrTyr

Tyr

DimerReceptor tyrosinekinase proteins(inactive monomers)

PPP

PP

P Tyr

TyrTyr

TyrTyr

TyrP

PP

PP

PCellularresponse 1

Inactiverelay proteins

Activatedrelay proteins

Cellularresponse 2

Activated tyrosine-kinase regions(unphosphorylateddimer)

Fully activated receptortyrosine-kinase(phosphorylateddimer)

6 ATP 6 ADP

Figure 11.7

Protein Kinaz Reseptörleri

ReseptörlerReseptörler

Cellularresponse

Gate open

Gate close

Ligand-gatedion channel receptor

Plasma Membrane

Signalmolecule(ligand)

Figure 11.7

Gate closed Ions

İyon Kanalı Reseptörleri

Reseptörlerin Reseptörlerin mekanizmalarımekanizmaları

Signal molecule

Activeproteinkinase

1

Activeproteinkinase

2

Activeproteinkinase

3

Inactiveprotein kinase

1

Inactiveprotein kinase

2

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

Cellularresponse

Receptor

P

P

P

ATPADP

ADP

ADP

ATP

ATP

PP

PP

PP

Activated relaymolecule

i

Phosphorylation cascade

P 

P

i

i

P

Fosforilasyon

Reseptörlerin Reseptörlerin mekanizmalarımekanizmaları

G proteini bağlanması

ATP

GTP

cAMP

Proteinkinase A

Cellular responses

G-protein-linkedreceptor

AdenylylcyclaseG protein

First messenger(signal moleculesuch as epinephrine)

İkincil İkincil HabercilerHaberciler

• Protein olmayan, küçük moleküller• Reseptörlerin aktifleşmesinde,

sinyalin iletilmesinde rol oynarlar.

– cAMP– Kalsiyum– İnositil trifosfat– Diaçilgliserol

PKA PKA AktivasyonuAktivasyonu

321

IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.

4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.

6 Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.

5

DAG functions asa second messengerin other pathways.

Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.

A signal molecule bindsto a receptor, leading toactivation of phospholipase C.

EXTRA-CELLULARFLUID

Signal molecule(first messenger)

G protein

G-protein-linkedreceptor

Variousproteinsactivated

Endoplasmicreticulum (ER)

Phospholipase CPIP2

IP3

(second messenger)

DAG

Cellularresponse

GTP

Ca2+

(second messenger)

Ca2+

IP3-gatedcalcium channel

Sinyal Sinyal ÇoğaltımıÇoğaltımı

Glucose-1-phosphate(108 molecules)

Glycogen

Active glycogen phosphorylase (106)

Inactive glycogen phosphorylase

Active phosphorylase kinase (105)

Inactive phosphorylase kinase

Inactive protein kinase A

Active protein kinase A (104)

ATP

Cyclic AMP (104)

Active adenylyl cyclase (102)

Inactive adenylyl cyclase

Inactive G protein

Active G protein (102 molecules)

Binding of epinephrine to G-protein-linked receptor (1 molecule)

Transduction

Response

Reception

HedeflerHedefler

• Gen anlatımı düzenleyicileri• Enzimler• Yapısal proteinler

Yavaş Yanıtlar

• Gen anlatımı üzerinde etkililerReception

Transduction

Response

mRNANUCLEUS

Gene

P

Activetranscriptionfactor

Inactivetranscriptionfactor

DNA

Phosphorylationcascade

CYTOPLASM

Receptor

Growth factor

Sinyal Sinyal KompleksleriKompleksleri

• Scaffold Proteinleri

Signalmolecule

Receptor

Scaffoldingprotein

Threedifferentproteinkinases

Plasmamembrane

Figure 11.16

RAS-MAPK RAS-MAPK YolağıYolağı

RAS Aktivasyonu

RAS-MAPK RAS-MAPK YolağıYolağı

MAPK Aktivasyonu

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