Cell Signaling• A __________________________is a series of steps by

which a signal on a cell’s surface is converted into a ________________________________________________

• Signal transduction pathways convert _________________ on a cell’s surface into _____________________________

AP Biology

Minzenmayer AP Biology Sig

nal

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wit

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Local vs. Long Distance Signaling

•Animal cells communicate using _____________________.•messenger molecules that travel only short distances

•long-distance signaling•plants and animals use chemicals called ____________________.

AP Biology

Minzenmayer AP Biology

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

Local Signaling w/o ____________________

Minzenmayer AP Biology ____

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Sig

nalin

g

AP Biology Lo

ng

-Dis

tan

ce _

____

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

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___________________________________

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?

AP Biology

Warm Up

AP Biology

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

Warm Up

AP Biology

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

Warm Up

AP Biology

Which diagram depicts long distance communication between cells?

Warm Up

AP Biology

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

AP Biology

AP Biology

Receptors in Plasma Membrane• three main types of membrane receptors:

• _______________________________________________

• _______________________________________________

• _______________________________________________

AP Biology

STEP 1: __________________________

____________________________________•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

_____________________

AP Biology

Minzenmayer AP Biology ____

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G proteins bind GTP

Fig. 11-7b

G protein-coupledreceptor

Plasmamembrane

Enzyme

G protein(inactive)

GDP

CYTOPLASM

Activatedenzyme

GTP

Cellular response

GDP

Pi

Activatedreceptor

GDP GTP

Signaling molecule

Inactiveenzyme

1 2

3

4

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

Tyrosine Kinases•Receptor tyrosine kinases

• membrane receptors that attach _________________ to tyrosines

• can trigger multiple signal transduction pathways at once

AP Biology

AP Biology Pro

tein

Kin

ase

& P

ho

sph

atas

e

P 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

Minzenmayer AP Biology

Tyrosine Kinase Receptor

Liga

nd R

ecep

tion

Rece

ptor

dim

eriz

ation

Phos

phor

yliz

ation

Protein

Activation

Tran

sduc

tion

Resp

onse

Ligand Gated Ion Channel

•ligand-gated ion channel receptor •acts as gate when __________________________ changes _______________.

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

AP Biology

Minzenmayer AP Biology

Ion

-Ch

ann

el R

ecep

tor

Reversibility is assured by

pumping ions back out again (using separate

protein)

AP Biology

Wrap-UpWould a hydrophobic molecule be expected to have an internal

or membrane receptor?

Intracellular Receptors• Some receptor proteins are intracellular

• found in ________________ or _________________of target cells

• Examples of messengers • steroid and thyroid _______________________ of animals

• An activated hormone-receptor complex can act as a _____________________________________________• turning on specific ____________________

AP Biology

Minzenmayer AP Biology

____

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Transduction•molecules that relay a signal from receptor to response are mostly ________________________.

•Like falling dominoes, receptor activates another protein, which activates another, …..until protein producing response is activated

•At each step, signal is _____________________ into a different form, usually a __________________ change in a protein

AP Biology

Protein Phosphorylation & Dephosphorylation

• In many pathways, signal is transmitted by cascade of protein ___________________________.

• Protein ____________________ transfer phosphates from ATP to protein, a process called ________________________________.

• Protein ____________________________ remove phosphates from proteins, a process called _____________________________.

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

AP Biology

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

______________________ Cascade

Activates protein kinase

Active PK1 transfers PFrom ATP to inactive PK2

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

Small Molecules & Ions Second Messengers• extracellular signal molecule that binds to receptor is a pathway’s

“___________________________________”

• _________________________________are

• small, nonprotein, water-soluble molecules or

• ions that spread throughout a cell by ____________________

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

• _____________________and __________________ ions are common second messengers

AP Biology

Cyclic AMP

•cAMP •widely used _________________________ messengers

•Adenylyl cyclase•converts _________________ to ________________ in response to extracellular signal

AP Biology

cAMP• Many signal molecules trigger formation of cAMP

• Other components of cAMP pathways are • ________________________

• G protein-coupled receptors

• ____________________________________

• 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

AP Biology

First messengerFig. 11-11

G protein

Adenylylcyclase

GTP

ATP

cAMPSecondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

cAM

P a

s a

____

____

____

_

Cell Signaling - Disease • Cholera

• Caused by Vibrio cholerae in contaminated water• Toxin secreted by V. cholerae in small intestine• Toxin modifies ______________________involved in salt/water

secretion • Can no longer hydrolyze GTP• Always __________________ - stimulates cAMP production

• Intestinal cells secrete water/ions• Severe 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

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

AP Biology

Nuclear & Cytoplasmic Responses• signal transduction pathway leads to

__________________ of one or more cellular activities• response may occur in

• cytoplasm or • may involve action in nucleus

• Many signaling pathways regulate synthesis of _________________• usually by turning genes on or off in nucleus

• final activated molecule may function as _________________________________

AP Biology

Fig. 11-14

Growth factor

Receptor

Phosphorylationcascade

Activetranscriptionfactor

P

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUS mRNA

GeneNu

clea

r R

esp

on

se

Fine Tuning Response

•Multistep pathways have two important benefits:• _________________________ signal

• and therefore the response• Contributing to ____________________ of response

•Signal Amplification• Enzyme cascades amplify cell’s response• At each step, number of activated products is much

greater than in preceding stepAP Biology

Minzenmayer AP Biology Sig

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(C

asca

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Minzenmayer AP Biology Sig

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asca

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WRAP-UP