AP Biology Minzenmayer

Cell Communication

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Cell Signaling A signal transduction pathway is a series of

steps by which a signal on a cell’s surface is converted into a specific cellular response

Signal transduction pathways convert signals on a cell’s surface into cellular responses

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Minzenmayer AP BiologySig

nal

ing

wit

h D

irec

t C

on

tact

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Local vs. Long Distance Signaling Animal cells communicate using local

regulatorsmessenger molecules that travel only short distances

long-distance signalingplants and animals use chemicals called hormones

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e.g., interferon release by viral-infected cells

Local Signaling w/o Direct Contact

Paracrine Signaling Synaptic Signaling

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Long

-Dis

tanc

e S

igna

ling

Hormone Signaling

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Lo

ng

-Dis

tan

ce D

iffu

sio

n Note how specificity is determined by presence/absence of receptor protein

Fig. 11-6-1

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Signal Transduction

Fig. 11-6-2

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Relay molecules in a signal transduction pathway

Transduction2

Signal Transduction

Fig. 11-6-3

EXTRACELLULARFLUID

Plasma membrane

CYTOPLASM

Receptor

Signalingmolecule

Relay molecules in a signal transduction pathway

Activationof cellularresponse

Reception Transduction Response1 2 3

Signal Transduction

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Signal Transduction

In this case the receptor protein is a membrane proteinLigan

d

Often turning on or off enzyme activity

Wrap-Up

How are receptor ligand interactions similar to enzyme substrate interactions?

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Warm Up

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In picture A, label the following:-cell-ligand-receptor-membrane channel

Warm Up

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Which diagram depicts communication between cells that are in close proximity?

Warm Up

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Which diagram depicts long distance communication between cells?

Warm Up

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In which type of communication would the ligand need to have the longest “life”?

What’s the point of Cell Communication??

Examples: Epinephrine stimulates the breakdown of

glycogen in mammals Temperature determines sex of some

vertebrate organisms DNA repair mechanisms

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How does cell communication work?

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Receptors in Plasma Membrane three main types of membrane receptors:

G protein-coupled receptorsReceptor tyrosine kinasesIon channel receptors

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STEP 1: RECEPTION

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G Proteins G protein-coupled receptor

plasma membrane receptor that works with the help of a G protein

G protein acts as an on/off switch: If GDP is bound to the G protein, G protein is inactive

AP Biology

Minzenmayer AP BiologyG-P

rote

in-L

inke

d R

ecep

tor

G proteins bind GTP

Fig. 11-7b

G protein-coupledreceptor

Plasmamembrane

EnzymeG protein(inactive)

GDP

CYTOPLASM

Activatedenzyme

GTP

Cellular response

GDP

P i

Activatedreceptor

GDP GTP

Signaling molecule

Inactiveenzyme

1 2

3 4

G-Protein-Linked ReceptorThe more ligand binding, the greater the cellular response

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Tyrosine Kinases Receptor tyrosine kinases

membrane receptors that attach phosphates to tyrosines

can trigger multiple signal transduction pathways at once

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Minzenmayer AP BiologyPro

tein

Kin

ase

& P

ho

sph

atas

eP r o te in O H + A T P P r o te in O P

O

O

O

+ A D P

P i H 2 O

P r o te in K in a s e

P r o te in P h o s p h a t a s e

reversibility of phosphorylation makes signaling

reversible

responses tend to

continue (or expand) only

so long as signaling continues

reversibility contributes

to the dynamic nature of

cells

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Tyrosine Kinase Receptor

Lig

an

d R

ece

pti

on

Re

cep

tor

dim

eri

zati

on

Ph

osp

ho

ryliz

atio

n

Protein

Activation

Tra

ns

du

ctio

n

Re

sp

on

se

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Ligand Gated Ion Channel ligand-gated ion channel receptor

acts as gate when receptor changes shape

When signal molecule binds as a ligand to receptor, gate allows specific ions, such as Na+ or Ca2+, through a channel in receptor

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Ion

-Ch

ann

el R

ecep

tor

Reversibility is assured by pumping ions

back out again (using

separate protein)

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Wrap-Up

Would a hydrophobic molecule be expected to

have an internal or membrane receptor?

Modeling Reception Work in groups of 3-4 Choose either G-Protein System or

Tyrosine-Kinase Receptor System Build a model Film your group “acting out” model –

think of this as a tutorial video for peers Email video to

ellen.quigley@springbranchisd.com Best videos will be uploaded to website

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Modeling Reception Use rest of class period today/finish after

school GOAL: model TODAY; film Friday Film due Friday @ end of class Questions due MONDAY 1/12/14

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QUIZ

1. What is local signaling?

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QUIZ

2. What is endocrine signaling?

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QUIZ

3. What are the three phases of cell signaling?

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QUIZ

4. How are intracellular receptors different from membrane receptors?

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QUIZ

5. What is the result of signal amplification?

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Intracellular Receptors Some receptor proteins are intracellular

found in cytosol or nucleus of target cells

Examples of messengers steroid and thyroid hormones of animals

An activated hormone-receptor complex can act as a transcription factor

turning on specific genes

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Fig. 11-8-1

Hormone(testosterone)

Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID

DNA

NUCLEUS

CYTOPLASM

Intr

acel

lula

r R

ecep

tor

Fig. 11-8-2

Receptorprotein

Hormone(testosterone)

EXTRACELLULARFLUID

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

Intr

acel

lula

r R

ecep

tor

Fig. 11-8-3

Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

Intr

acel

lula

r R

ecep

tor

Fig. 11-8-4

Hormone(testosterone)

EXTRACELLULARFLUID

PlasmamembraneReceptor

protein

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

Intr

acel

lula

r R

ecep

tor

Fig. 11-8-5

Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS New protein

CYTOPLASM

Intr

acel

lula

r R

ecep

tor

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Intr

acel

lula

r R

ecep

tor

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Transduction molecules that relay a signal from

receptor to response are mostly proteins Like falling dominoes, receptor activates

another protein, which activates another, …..until protein producing response is activated

At each step, signal is transduced into a different form, usually a shape change in a protein

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Protein Phosphorylation & Dephosphorylation

In many pathways, signal is transmitted by cascade of protein phosphorylations

Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

Protein phosphatases remove phosphates from proteins, a process called dephosphorylation

phosphorylation and dephosphorylation system acts as molecular switch, turning activities on and off

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Signaling molecule

Receptor Activated relaymolecule

Inactiveprotein kinase1

Activeproteinkinase1

Inactiveprotein kinase2

ATPADP

Activeproteinkinase2

P

PPP

Inactiveprotein kinase3

ATPADP Active

proteinkinase3

P

PPP

i

ATPADP P

ActiveproteinPP

P i

Inactiveprotein

Cellularresponse

Phosphorylation cascade

i

Phosphorylation Cascade

Activates protein kinase

Active PK1 transfers PFrom ATP to inactive PK2

Protein phosphatases (PP) catalyze removal of P to make them inactive again

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Small Molecules & Ions Second Messengers

extracellular signal molecule that binds to receptor is a pathway’s “first messenger”

Second messengers are small, nonprotein, water-soluble molecules or

ions that spread throughout a cell by diffusion

participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases

Cyclic AMP and calcium ions are common second messengers

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Cyclic AMP cAMP

widely used second messengers Adenylyl cyclase

converts ATP to cAMP in response to extracellular signal

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cAMP Many signal molecules trigger formation of cAMP Other components of cAMP pathways are

G proteins

G protein-coupled receptors

protein kinases

cAMP usually activates protein kinase A, which phosphorylates various other proteins

Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase

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First messengerFig. 11-11

G protein

Adenylylcyclase

GTP

ATP

cAMPSecondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

cAM

P a

s a

2nd

Mes

sen

ger

Cell Signaling - Disease Cholera

Caused by Vibrio cholerae in contaminated waterToxin secreted by V. cholerae in small intestineToxin modifies G protein involved in salt/water secretion

Can no longer hydrolyze GTPAlways active - stimulates cAMP production

Intestinal cells secrete water/ionsSevere diarrhea

often lethal due to dehydration and salt imbalance

Cell Signaling - Cholera

H2O, ions

H2O, ionsGDPGTP

Toxinactive inactive

Intestinal Cell

Ext

Int

Net Effect

Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

cAMP

Intestinal Lumen

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Calcium Ions & Inositol Triphosphate (IP3)

Calcium ions (Ca2+) act as a second messenger in many pathways

Calcium is an important second messenger because cells can regulate its concentration

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Nuclear & Cytoplasmic Responses signal transduction pathway leads to

regulation of one or more cellular activities response may occur in

cytoplasm or may involve action in nucleus

Many signaling pathways regulate synthesis of proteins

usually by turning genes on or off in nucleus final activated molecule may function as

transcription factor

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Fig. 11-14Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor

ResponseP

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUS mRNA

GeneNu

clea

r R

esp

on

se

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Fine Tuning Response Multistep pathways have two important

benefits:Amplifying signal

and therefore the response

Contributing to specificity of response Signal Amplification

Enzyme cascades amplify cell’s response

At each step, number of activated products is much greater than in preceding step

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Minzenmayer AP BiologySig

nal

Am

plif

icat

ion

(C

asca

de)

Minzenmayer AP BiologySig

nal

Am

plif

icat

ion

(C

asca

de)

Fig. 11-UN1

Reception Transduction Response

Receptor

Relay molecules

Signalingmolecule

Activationof cellularresponse

1 2 3

WRAP-UP