Ch26 Cell Signalling

Yuki Juan

NTU

May 19, 2003

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

Term Definition

Second messengers: A small intracellular regulatory molecules which

causes cell responses. E. g. Cyclic AMP

Outline of Receptor-mediated Signalling

Target cell

receptor

Cellular Responses to Singals

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

What Are The Singalling Molecules Neurotransmitters Endocrine Howmones: (Table 26.1)

The “classical” singalling molecules Growth factors and cytokines

Regarded as singals Which may induce cell growth and division or inhibit it May affect differentiation Instruct the cell to undergo apoptosis

Vitamins A and D derivatives Retinoic acid (Vit A): singalling molecule in embryonic deve

lopment and normal cell growth Vitamin D3: control of genes involved in calcium absorption

from the intestine

How Hormone Binding To Surface Receptor

Growth Factors and Cytokines Most cytokines/growth factors are paracrine,

some are autocrine The first known growth factor was platelet-der

ived growth factor (PDGF) PDGF stimulates cell division and repair

Epidermal growth factor (EGF) stimulates the growth of Skin cells

Colony stimulating factors (CSFs) Stimulate the growth of colonies of white cells on t

he culture plates.

Autocrine Singals and Paracrine Signals

Autocrine signals affect the cell producing them. Paracrine singals diffuse only a short distance to

affect nearby cells

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

The Structures of the Lipid-soluble signalling Molecules They can combine

with their specific receptors which exist inside the cell rather than in the membrane

Gene Activation by Steroid Hormones The glucocorticoid

receptor: one of a superfamily of steroid/thyroxine receptors

Binding to DNA sites by zinc fingers

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

Central Principle of Control by Many Extracellular Signals Key processes in cell si

gnalling are protein phosphorylation by protein kinases and reversal by protein phosphatases

Tyrosine Phosphorylation by Tyrosine Kinase

Tyrosine Kinase Type of Receptors and The Other Type of Signalling

Adaptor molecules

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

Tyrosine Kinase-associated Receptors Ras signal transduction pathway

Ras : a protein exits in all eukaryotic cells There are no small molecular weight second mes

sengers in this pathway—all of the components are proteins

Ras was discovered as the oncogenic protein coded for by the rat sarcoma virus

Phosphatidylinositide 3-kinase pathway JAK/STAT protein-associated receptor

The Ras Singal Transduction Pathway

Raf, MEK and ERK: mitogen-activated protein kinases (MAP) kinases

Raf: rat sarcoma; MAPKKK MEK: Map kinase/ERK; MAPKK ERK: extracellular siganl-regulat

ed protien kinase; MAPK

The Ras Singal Transduction Pathway

The Control of The Ras Protein

A Rapid Molecular Switch Mechanism

Multiple Signal Pathways Of The Ras Type

Phosphatidylinositide 3-kinase Pathway PI 3 kinase involved in

Cell proliferation Differentiation Other cellular activities including metabolic control

Insulin

Simplified Insulin Singalling Pathway

IRS: insulin receptor substratePKB: protein kinase B

Production of The Second Messenger

JAK/STAT Protein-associated Receptor Interferons

A protective proteins released by cells infected by virus

STAT proteins Singal transducer and activator of transcription SH2 domains bind to the phosphorylated receptor

s JAK kinase:

Janus kinase Has two catalytic sites

The Singalling Pathway by Which -interferon Activates Specific Gene Transcription

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

The G-protein-coupled Receptors G protein:

Heterotrimeric A protein made up of three different subunits:,

, G protein receptor have no enzymic activity

The Structure of The 2-adrenergic Recptor

cAMP

The Control of Adenylate Cyclase Activity by a Hormone Such As Epinephrine

The 2-adrenergic Recptor Function PKA: protein kina

se A CREB: cAMP res

ponse element binding protein

CRE: cAMP response element of gene promoter

Hydrolysis of Phosphatidylinositol-4, 5-bisphosphate

The Phosphatidylinositol Cascade

Phorbol EstersTumor-promoting effect

Structure of a Rod Cell

The Structures of Light Singal Molecules

The G-protein-coupled Receptor Involved In Vision

Simplified Diagram of The Visual Process

Outline

Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling syste

ms Tyrosine kinase-associated receptors The G-protein-coupled receptors Singal transduction pathway using cGMP as

second messenger

Formation of 3’,5’–cyclic GMP

Production of The Second Messenger cGMP by Two Routes

Simplified Summary Diagram of The Singal Transduction Pathways

Ch28 Virus and Viroids

Yuki Juan

Virus

Much smaller It generates no energy and catalyses no reac

tions Structure simple

Genetic materials: DNA or RNA Protein

病毒的區分 依外觀區分 依遺傳物質區分

How Are Virus Get Into Cells ? The receptor-mediated endo

cytosis

Bacterial Virus (Bacteriophages)

Types of Genetic Material in Different Virus

Double-stranded DNA Single-stranded DNA Double-stranded RNA Single-stranded RNA

(+)sense RNA (-)non-sense RNA

Why can some virues get away with having RNA as genetic material That viral genomes are exceeding small therefore the chances of deleterious

mutations during replication of viral RNA are smaller.

Rapid mutation helps the virus to escape immunological attack by the animal host.

Double-stranded DNA Viruses

Transcribed by host RNA polymerase

Double-strand RNA Viruses

RNA-dependent RNA polymerases Translation by the host cell machinery

Single-stranded RNA Viruses

(+)sense RNA (HIV) The protein synthesizing machinery of the cell can

immediately translate it into proteins (-)non-sense RNA

An additional RNA-replicating enzyme is needed

Release of Viral Particles

Vaccinia

Double-stranded DNA viruses Own RNApolymerase

Polioviurs

Naked virion: it has only a nucleocapsid shell of coat protein but no membrane)

(+)single-strand RNA Producing an RNA replicase Polyprotein: a single largeprotein

Influenza virus

(-) strand RNA virus

Retrovirus

Bacteriophage lambda