Ch26 Cell Signalling
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Ch26 Cell Signalling
Yuki Juan
NTU
May 19, 2003
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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
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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
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Term Definition
Second messengers: A small intracellular regulatory molecules which
causes cell responses. E. g. Cyclic AMP
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Outline of Receptor-mediated Signalling
Target cell
receptor
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Cellular Responses to Singals
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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
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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
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How Hormone Binding To Surface Receptor
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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.
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Autocrine Singals and Paracrine Signals
Autocrine signals affect the cell producing them. Paracrine singals diffuse only a short distance to
affect nearby cells
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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
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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
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Gene Activation by Steroid Hormones The glucocorticoid
receptor: one of a superfamily of steroid/thyroxine receptors
Binding to DNA sites by zinc fingers
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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
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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
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Tyrosine Phosphorylation by Tyrosine Kinase
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Tyrosine Kinase Type of Receptors and The Other Type of Signalling
Adaptor molecules
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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
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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
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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
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The Ras Singal Transduction Pathway
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The Control of The Ras Protein
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A Rapid Molecular Switch Mechanism
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Multiple Signal Pathways Of The Ras Type
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Phosphatidylinositide 3-kinase Pathway PI 3 kinase involved in
Cell proliferation Differentiation Other cellular activities including metabolic control
Insulin
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Simplified Insulin Singalling Pathway
IRS: insulin receptor substratePKB: protein kinase B
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Production of The Second Messenger
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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
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The Singalling Pathway by Which -interferon Activates Specific Gene Transcription
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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
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The G-protein-coupled Receptors G protein:
Heterotrimeric A protein made up of three different subunits:,
, G protein receptor have no enzymic activity
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The Structure of The 2-adrenergic Recptor
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cAMP
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The Control of Adenylate Cyclase Activity by a Hormone Such As Epinephrine
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The 2-adrenergic Recptor Function PKA: protein kina
se A CREB: cAMP res
ponse element binding protein
CRE: cAMP response element of gene promoter
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Hydrolysis of Phosphatidylinositol-4, 5-bisphosphate
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The Phosphatidylinositol Cascade
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Phorbol EstersTumor-promoting effect
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Structure of a Rod Cell
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The Structures of Light Singal Molecules
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The G-protein-coupled Receptor Involved In Vision
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Simplified Diagram of The Visual Process
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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
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Formation of 3’,5’–cyclic GMP
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Production of The Second Messenger cGMP by Two Routes
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Simplified Summary Diagram of The Singal Transduction Pathways
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Ch28 Virus and Viroids
Yuki Juan
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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
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How Are Virus Get Into Cells ? The receptor-mediated endo
cytosis
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Bacterial Virus (Bacteriophages)
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Types of Genetic Material in Different Virus
Double-stranded DNA Single-stranded DNA Double-stranded RNA Single-stranded RNA
(+)sense RNA (-)non-sense RNA
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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.
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Double-stranded DNA Viruses
Transcribed by host RNA polymerase
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Double-strand RNA Viruses
RNA-dependent RNA polymerases Translation by the host cell machinery
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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
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Release of Viral Particles
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Vaccinia
Double-stranded DNA viruses Own RNApolymerase
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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
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Influenza virus
(-) strand RNA virus
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Retrovirus
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Bacteriophage lambda