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300104 Dr. La-iad Nakkrasae4. Cell communication

(multicellular organisms)

Saccharomyces cerevisiae ( 4-1) 2 a a factor

(receptor) factor a 2 factors 2

2 /a 2

4-1 (Campbell and Reece, 2002)

a factor factor?

factor ligand signal-transduction pathway signal transduction 2

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300104 Dr. La-iad NakkrasaeCommunicating cells may be close together or far apart

chemicalmessenger (target cell) chemical messenger

growth factor

paracrine signaling (Neurotransmitter) ( 4-2a) (endocrine signaling)

( 4-2b)

4-2 Local and long-distance cell communication in animals (Campbell and Reece, 2002)

cell junction junction cytoplasm 2 cytosol 2 ( 4-3a) ( 4-3b) ligand

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300104 Dr. La-iad Nakkrasaetransduced

4-3a Cell junction celljunction 2

(Campbell and Reece, 2002)

4-3b cell-cell recognition 2

(Campbell and Reece, 2002)

3 cell signaling.. 1971 Earl W. Sutherland Nobel Prize chemical signaling

signal-transduction pathway epinephrine glycogen glycogen glucose-6-phosphate glycolysis

glucose-1-phosphale glucose

Sutherland epinephrine glycogen glycogen phosphorylase epinephrine glycogen glycogen phosphorylase glycogen glycogenphosphorylase

epinephrine glycogen phosphorylase intermediate step enzyme epinephrine glycogen phosphorylase

Sutherland 3 ( 4-4)

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300104 Dr. La-iad Nakkrasae1. Reception chemical messenger

ligand

2. Transduction chemical messenger transduction transduction Sutherland epinephrine glycogen

3. Response enzyme cytoskeleton

4-4 Overview of cell signaling (Campbell and Reece, 2002)

Signal reception and the initiation of transduction

yeast a yeast epinephrine epinephrine

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300104 Dr. La-iad Nakkrasae Chemical messenger

(receptor) 3 1.G-protein-linked Receptor -helix 7 (

4-5) epinephrine mating factor G protein-linked receptor binding site chemical messenger

4-5 G-protein-linked receptor-helix (Campbell andReece, 2002)

chemical messenger G-protein-linked receptor cytoplasm G protein switch - GDP GTP GDP switch G protein inactive ( 4-6a) GTP active form ( 4-6b) G protein active form chemical messenger GTPase phosphate GTP GDP G protein inactive form ( 4-6c) G protein (embryonic development) G protein

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300104 Dr. La-iad Nakkrasae G protein Gprotein cholera, Prussic Botulism

60% G protein pathway

4-6a G-protein system in inactive form (Campbell and Reece, 2002)

4-6b G-protein system in active form (Campbell and Reece, 2002)

4-6c Return to inactive form (Campbell and Reece, 2002)

2.Tyrosine-kinase receptor

Growth factor growth factor tyrosine kinase receptor

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300104 Dr. La-iad Nakkrasaereceptor ligand cytoplasm tyrosine kinase receptor tyrosine kinase phosphate ATP tyrosine substrate

protein phosphate growth factor tyrosine-kinase receptor inactiveform Helix binding site tyrosine ( 4-7a) receptor

4-7 tyrosine-kinase receptor signal molecule(Campbell and Reece, 2002)

1. Signal molecules binding site Tyrosine-kinase receptor Tyrosine-kinasereceptor dimer (2 polypeptide) ( 4-7b)

2. dimer tyrosine kinase 2 polypeptides tyrosine kinase phosphate tyrosine polypeptide receptor

3. phosphorylated tyrosine phosphate

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300104 Dr. La-iad Nakkrasae dimer tyrosine-kinase receptor intracellular protein 10

4. Transduction pathways receptor 1 pathways tyrosine-kinase receptor G protein-linked receptor

3.IonChannel Receptors channel protein - Na+ K+ channel chemical messenger channel ion ion channel channel ( 4-8)

chemical messenger signaling molecule binding site Ion-channel receptor Na+ gate Na+ channel Na+ channel

4-8 A ligand-gated ion-channel receptor (Campbell and Reece, 2002)

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300104 Dr. La-iad NakkrasaeIntracellular Receptor

(Receptor) cytosol chemical messenger

chemical messenger

hydrophobic

steroid hormone

thyroid hormone chemical messenger NO

4-9 testosterone steroid hormone testosterone cytoplasm nucleus transcription factor intracellular receptor testosterone

4-9 Steriod hormone interacting with an intracellular receptor (Campbell and Reece, 2002)

Signal transduction pathways

Signal receptor (transduction) extracellular signal

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300104 Dr. La-iad Nakkrasaemolecule Pathways relay signals from receptors to cellular responses

Protein phosphorylation

signal transduction

protein receptor Phosphate tyrosine tyrosine kinase enzyme phosphate ATP protein kinase proteinkinase cytoplasm tyrosine kinase phosphate serine threonine substrate serine/threonine kinase fungi

Protein kinase ( 4-10) growth factor growth factor 0t protein kinase 1 phosphate inactive form activeform protein kinase phosphorylation cascade phosphate protein active inactive form

4-10 A phosphorylation cascade (Campbell and Reece, 2002)

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300104 Dr. La-iad Nakkrasae Protein kinase 1%

protein kinase 1 protein kinase 100 substrate protein protein

pathway Signal transduction enzyme

protein phosphatase phosphate inactive protein protein kinase proteinphosphatase

Secondary messengers

Signal transduction pathway ion secondary messenger ( chemicalmessenger first messenger) secondary messengers cyclic AMP (cAMP) Ca2+

Cyclic AMP (cAMP)

Sutherland epinephrine glycogen epinephrine

secondary messenger cytoplasm epinephrine cAMP ( cAMP 4-11) enzyme Adenylyl cyclase ATP cAMP enzyme first messenger hormone membrane enzyme cAMP Cytoplasm Hormone cAMP AMP inactive form cAMP

protein kinase A ( 4-12) serine/thrones kinase protein kinase

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300104 Dr. La-iad Nakkrasae

4-11 Cyclic AMP (cAMP) ATP enzyme Adenyly cyclase (Campbell and Reece,2002)

Secondary messenger cAMP G-protein signaling pathway Vibrio cholerae

bacteria G protein G protein GTP GDP G protein active form

4-12 cAMP secondary messenger (Campbell and Reece, 2002)

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300104 Dr. La-iad NakkrasaeCalcium ions and Inosital Trisphosphate

Growth factor signal transduction Ca2+ secondarymessenger

cAMP

Ca2+ secondary messenger Ca2+ secondary messenger G-proteinpathway tyrosine-kinase pathway

Ca2+ Ca2+ extracellular fluid 10,000 Ca

2+ endoplasmic reticulum active transport (

mitochondria chloroplast) Ca2+

ER cytosol signal transduction Ca2+ cytosol Ca2+ ER Ca2+ secondarymessenger diacylglycerol (DAG) inositol triphosphate (IP3) 2 phospholipids ( 4-13) IP3 Ca

2+

ER IP3 Ca2+ Ca2+ third

messenger secondary messenger

signal transduction pathway

4-13 Calcium and inositol trisphosphate in signaling pathways (Campbell and Reece, 2002)

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300104 Dr. La-iad Nakkrasae

Ca2+ signal transduction protein Calmodulin Ca2+ binding protein Ca2+

Ca2+

Calmodulin

Cellular responses to signals

Signal transduction cytoplasm - ion channel palma membrane cell metabolism

epinephrine metabolism glycogen 4-14 pathway epinephrine

4-14 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine(Campbell and Reece, 2002)

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300104 Dr. La-iad Nakkrasae

enzyme enzyme nucleus 4-15 signaling

pathway transcription factor growth factor mRNA translate transcription factor transcriptionfactor

4-15 The specificity of cell signaling (Campbell and Reece, 2002)