Fig. 11-1 Figure 11.1 How do the effects of Viagra (multicolored) result from its inhibition of a signaling-pathway enzyme (purple)?

Yeast cell, mating type a Yeast cell, mating type  Fig. 11-2  factor Receptor 1 Exchange of mating factors a  a factor Yeast cell, mating type a Yeast cell, mating type  2 Mating a  Figure 11.2 Communication between mating yeast cells New a/ cell a/ 3

1 Individual rod- shaped cells 2 Aggregation in process 3 Fig. 11-3 1 Individual rod- shaped cells 2 Aggregation in process 0.5 mm 3 Spore-forming structure (fruiting body) Figure 11.3 Communication among bacteria Fruiting bodies

Gap junctions between animal cells Plasmodesmata between plant cells Fig. 11-4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions Figure 11.4 Communication by direct contact between cells (b) Cell-cell recognition

Figure 11.5 Local and long-distance cell communication in animals Local signaling Long-distance signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Endocrine cell Blood vessel Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Hormone travels in bloodstream to target cells Local regulator diffuses through extracellular fluid Target cell is stimulated Target cell Figure 11.5 Local and long-distance cell communication in animals (a) Paracrine signaling (b) Synaptic signaling (c) Hormonal signaling

Plasma membrane 1 Reception Transduction Response Receptor Activation Fig. 11-6-3 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling Signaling molecule

Signaling-molecule binding site Fig. 11-7a Signaling-molecule binding site Figure 11.7 Membrane receptors—G protein-coupled receptors, part 1 Segment that interacts with G proteins G protein-coupled receptor

Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2 Fig. 11-7b Plasma membrane G protein-coupled receptor Inactive enzyme Activated receptor Signaling molecule GDP G protein (inactive) Enzyme GDP GTP CYTOPLASM 1 2 Activated enzyme Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2 GTP GDP P i Cellular response 3 4

Fully activated receptor tyrosine kinase Fig. 11-7c Signaling molecule (ligand) Ligand-binding site Signaling molecule  Helix Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins Dimer CYTOPLASM 1 2 Activated relay proteins Figure 11.7 Membrane receptors—receptor tyrosine kinases Cellular response 1 Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Cellular response 2 Tyr Tyr P Tyr Tyr P Tyr P Tyr P 6 ATP 6 ADP Activated tyrosine kinase regions Fully activated receptor tyrosine kinase Inactive relay proteins 3 4

1 Signaling molecule (ligand) Gate closed Ions Plasma membrane Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane Ligand-gated ion channel receptor 2 Gate open Cellular response Figure 11.7 Membrane receptors—ion channel receptors 3 Gate closed

Hormone (testosterone) Plasma membrane Receptor protein Hormone- Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS New protein CYTOPLASM

Phosphorylation cascade Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP Active protein kinase 2 P PP P i Figure 11.9 A phosphorylation cascade Inactive protein kinase 3 ATP ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i

Fig. 11-10 Figure 11.10 Cyclic AMP Adenylyl cyclase Phosphodiesterase Pyrophosphate P P i ATP cAMP AMP Figure 11.10 Cyclic AMP

First messenger Adenylyl cyclase G protein GTP G protein-coupled Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP Figure 11.11 cAMP as second messenger in a G-protein-signaling pathway Protein kinase A Cellular responses

EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Fig. 11-12 EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Figure 11.12 The maintenance of calcium ion concentrations in an animal cell Ca2+ pump ATP Key High [Ca2+] Low [Ca2+]

EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein Fig. 11-13-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Figure 11.13 Calcium and IP3 in signaling pathways Endoplasmic reticulum (ER) Various proteins activated Cellular responses Ca2+ Ca2+ (second messenger) CYTOSOL

Growth factor Reception Receptor Phosphorylation cascade Transduction Fig. 11-14 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor Response P DNA Gene NUCLEUS mRNA

Glucose-1-phosphate (108 molecules) Fig. 11-15 Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Figure 11.15 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules)

Fig. 11-17 Figure 11.17 The specificity of cell signaling Signaling molecule Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses. Figure 11.17 The specificity of cell signaling Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Signaling Plasma molecule membrane Receptor Three different protein Fig. 11-18 Signaling molecule Plasma membrane Receptor Three different protein kinases Figure 11.18 A scaffolding protein Scaffolding protein

Fig. 11-19 Figure 11.19 Apoptosis of human white blood cells 2 µm

Figure 11.20 Molecular basis of apoptosis in C. elegans Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Ced-4 Ced-3 Receptor for death- signaling molecule Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Death- signaling molecule Figure 11.20 Molecular basis of apoptosis in C. elegans Active Ced-4 Active Ced-3 Other proteases Nucleases Activation cascade (b) Death signal

Interdigital tissue 1 mm Fig. 11-21 Figure 11.21 Effect of apoptosis during paw development in the mouse

Reception Transduction Response Receptor Activation of cellular Fig. 11-UN1 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules Signaling molecule

Fig. 11-UN2

You should now be able to: Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels List two advantages of a multistep pathway in the transduction stage of cell signaling Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Define the term second messenger; briefly describe the role of these molecules in signaling pathways Explain why different types of cells may respond differently to the same signal molecule Describe the role of apoptosis in normal development and degenerative disease in vertebrates Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings