I.Signal Transduction Pathways II.Signaling ranges III.Three receptor classes (families) IV.Intracellular receptors V.Phosphorylation cascades VI.Second.

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