I. Signal Transduction Pathways

II. Signaling ranges

III. Three receptor classes (families)

IV. Intracellular receptors

V. Phosphorylation cascades

VI. Second messengers

VII. Signal efficiency

VIII. Apoptosis

IX. Summary

Lecture 8 Outline (Ch. 11)

Cell Signaling = Signal Transduction

Signal Transduction – receiving a signal & relaying the response

Reception Transduction Response

Receptor

Relay molecules

Signalingmolecule

Activationof cellularresponse

1 2 3

Signal Transduction

Cell phone rings You listen to your friend

You drive somewhere

Response variable – examples: mate, organize, divide, die, grow, send another signal, etc…

Sending the Signal – direct contact

Sending the Signal

Three methods of cell signaling over distances:

Signal Transduction

Signaling-molecule binding site

Segment thatsends signal inside cell

The receptor is a protein that detects the signal

Signal called a ligand

G-protein coupled receptors (GPCRs)

A 7-pass transmembrane receptor

Links via a G-protein….binds GTP/GDP

Receptor Tyrosine Kinases (RTKs)

Transmembrane receptor – dimerizes when activated

Auto-phosphorylates when active to rely signal

Ligand-gated ion channels

Open when the ligand is bound

Close when signal is not present

Signal Transduction for hydrophobic molecules

Receptorprotein

Hormone(testosterone)

EXTRACELLULARFLUID

Plasmamembrane

Hormone-receptorcomplex

DNA

Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

• hydrophobic signals

- Receptor moves to DNA

Transduction – relay the signal

• Phosphorylation: adding a phosphate group

• Used to activate proteins already in the cell

Transduction hydrophilic signals – relay the signal

• Dephosphorylation = removing a phosphate group

Signaling molecule

ReceptorActivated relaymolecule

Inactiveprotein kinase

1 Activeproteinkinase

1

Inactiveprotein kinase

2

ATPADP Active

proteinkinase

2

P

PPP

Inactiveprotein kinase

3

ATPADP Active

proteinkinase

3

P

PPP

i

ATPADP P

ActiveproteinPP

P i

Inactiveprotein

Cellularresponse

Phosphorylation cascadei

• hydrophilic signals

Receptor alerts molecules inside the cell = phosphorylation

Signal Transduction for hydrophilic molecules

First messenger

G proteinAdenylylcyclase

GTP

ATPcAMP

Secondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

• Or use second messengers

= small molecules inside cell to relay message

• example second messengers: GTP, cAMP, ATP, Ca++

Signal Transduction for hydrophilic molecules

Specificity of cell signaling

Scaffold proteins increase signal efficiency

• Scaffold protein – larger protein for binding and bringing together several other signal proteins

Interdigital tissue

1 mm

Response – cell does something

protein (active)Inhibits activity

Mitochondrion

Receptorfor death-signalingmolecule

Inactive proteins

(a) No death signal

Response – ex. No death signal, cell lives

Apoptosis – programmed cell death

- membrane inverts- biomolecules degraded- organelles break down

(b) Death signal

Death-signalingmolecule

(inactive)Cellformsblebs

Active Active

Activationcascade

Otherproteases

Nucleases

Response – ex. Death signal, cell undergoes apoptosis

Caspases

Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor

ResponseP

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUS mRNA

Gene

Signal transduction = reception, transduction, response