Cell Communication

Chapter 7

7.1 Cell Communication: An Overview

Cells communicate with one another through • Direct channels of communication

• Specific contact between cells

• Intercellular chemical messengers

Apoptosis

Fig. 7-1, p. 140

Intercellular Chemical Messengers

Controlling cell• Releases signal molecule that causes response

of target cells

Target cell processes signal in 3 steps:• Reception, transduction, response

Signal transduction • Series of events from reception to response

Signal Transduction

Fig. 7-2, p. 142

Reception

7.2 Cell Communication Systems with Surface Receptors

Peptide hormones and neurotransmitters• Primary extracellular signal molecules recognized

by surface receptors in animals

Surface receptors• Integral membrane glycoproteins

Signaling molecule• Bound by a surface receptor

• Triggers response pathways within the cell

Surface Receptors

Cell communication systems based on surface receptors have 3 components: (1) Extracellular signal molecules

(2) Surface receptors that receive signals

(3) Internal response pathways triggered when receptors bind a signal

Peptide Hormones

Peptide hormones • Small proteins

Growth factors• Special class of peptide hormones

• Affect cell growth, division, differentiation

Neurotransmitters

Neurotransmitters include• Small peptides

• Individual amino acids or their derivatives

• Chemical substances

Surface Receptors

Surface receptors• Integral membrane proteins

• Extend entirely through the plasma membrane

Binding of a signal molecule• Induces molecular change in the receptor that

activates its cytoplasmic end

Response of Surface Receptor

Cellular Response Pathways (1)

Cellular response pathways• Operate by activating protein kinases

Protein kinases add phosphate groups• Stimulate or inhibit activities of target proteins,

producing cellular response

Cellular Response Pathways (2)

Protein phosphatases• Reverse response

• Remove phosphate groups from target proteins

Receptors are removed by endocytosis• When signal transduction is finished

Phosphorylation

Amplification

Each step of a response pathway catalyzed by an enzyme is amplified• Each enzyme activates hundreds or thousands of

proteins that enter next step in pathway

Amplification • Allows full cellular response when few signal

molecules bind to receptors

Amplification

7.3 Surface Receptors with Built-In Protein Kinase Activity

Receptor Tyrosine Kinases

Receptor Tyrosine Kinases

Receptor tyrosine kinases bind signal molecule• Protein kinase site becomes active

• Adds phosphate groups to tyrosines in the receptor itself, and to target proteins

Phosphate groups added to cytoplasmic end of receptor are recognition sites for proteins activated by binding to the receptor

Protein Kinase Activity

7.4 G-Protein–Coupled Receptors

G proteins: Key molecular switches in second-messenger pathways

Two major G-protein–coupled receptor response pathways involve different second messengers

G-Protein-Coupled Receptors

G-protein-coupled receptors activate pathways • Binding of the extracellular signal molecule (first

messenger) activates a site on the cytoplasmic end of the receptor

G-Protein-Coupled Receptors

Fig. 7-8, p. 147

G-Protein Activation

Activated receptor turns on a G protein, which acts as a molecular switch

G protein• Active when bound to GTP

• Inactive when bound to GDP

Active G Protein

Active G protein • Switches on the effector of the pathway (enzyme

that generates second messengers)

Second messengers • Small internal signal molecules

• Activate the protein kinases of the pathway

Response Pathways

Second Messengers: cAMP

1st of two major pathways triggered by G-protein-coupled receptors

Effector (adenylyl cyclase) generates cAMP as second messenger

cAMP activates specific protein kinases

cAMP Receptor-Response Pathways

Fig. 7-10, p. 148

cAMP

Fig. 7-11, p. 148

Second Messengers: IP3 and DAG (1)

2nd major pathway triggered by G-protein–coupled receptors

Activated effector (phospholipase C), generates two second messengers, IP3 and DAG

Second Messengers: IP3 and DAG (2)

IP3 activates transport proteins in the ER

• Releasing stored Ca2+ into the cytoplasm

Released Ca2+ (alone or with DAG) activates specific protein kinases • Adds phosphate groups to target proteins

IP3/DAG Receptor-Response Pathways

Pathway Controls

cAMP and IP3/DAG pathways are balanced by reactions that eliminate second messengers• Stopped by protein phosphatases that continually

remove phosphate groups from target proteins

• Stopped by endocytosis of receptors and their bound extracellular signals

Mutations

Mutated systems can turn on the pathways permanently, contributing to progression of some forms of cancer

Gene Regulation: Ras

Some pathways in gene regulation link certain receptor tyrosine kinases to a specific G protein (Ras)

When the receptor binds a signal molecule, it phosphorylates itself• Adapter proteins then bind, bridging to and

activating Ras

Activated Ras

Activated Ras turns on the MAP kinase cascade

Last MAP kinase in cascade phosphorylates target proteins in the nucleus• Activates them to turn on specific genes

Many of these genes control cell division

Gene Regulation

7.5 Pathways Triggered by Internal Receptors: Steroid Hormone Receptors

Steroid hormones have widely different effects• Depend on relatively small chemical differences

Response of a cell to steroid hormones• Depends on internal receptors and the genes

they activate

Steroid Hormone Receptors

Steroid hormones penetrate plasma membrane • Bind to receptors within the cell

Internal receptors• Regulatory proteins that turn on specific genes

when activated by binding a signal molecule

• Produce cellular response

Two Domains of Steroid Hormone Receptors

Steroid hormone receptors• One domain recognizes and binds a specific

steroid hormone

• One domain interacts with the controlling regions of target genes

Gene Activation: Steroid Hormone Receptors

Cell Response

Cell response to a steroid hormone• Depends on whether it has an internal receptor

for the hormone

Type of response within the cell• Depends on the genes that are recognized and

turned on by an activated receptor

7.6 Integration of Cell Communication Pathways

Cross talk

Cross-Talk

Cell signaling pathways communicate with one another to integrate responses to cellular signals

May result in a complex network of interactions between cell communication pathways

Cross-Talk

Modification of Cell Response

Cross-talk often results in • Modifications of cellular responses controlled by

the pathways

• Fine-tuning effects of combinations of signal molecules binding to receptors of a cell

Cell Communication PathwaysIn Animals

Inputs from other cellular response systems also can become involved in the cross-talk network• Cell adhesion molecules

• Molecules arriving through gap junctions