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Ch26 Cell Signalling. Yuki Juan NTU May 19, 2003. Outline. Introduction What are the singalling molecules Intracellular receptor-mediated responses Membrane receptor-mediated singalling systems Tyrosine kinase-associated receptors The G-protein-coupled receptors - PowerPoint PPT Presentation
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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
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