Alberts • Johnson • Lewis • Morgan • Raff • Roberts • Walter
Molecular Biology
of the Cell
Sixth Edition
Chapter 15
Cell Signaling
Copyright © Garland Science 2015
CHAPTER CONTENTS
PRINCIPLES OF CELL SIGNALING
SIGNALING THROUGH G-PROTEIN-COUPLED
RECEPTORS
SIGNALING THROUGH ENZYME-COUPLED
RECEPTORS
ALTERNATIVE SIGNALING ROUTES IN GENE
REGULATION
SIGNALING IN PLANTS
GPCR Desensitization Depends on Receptor Phosphorylation
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Activated Receptor Tyrosine Kinases (RTKs)
Phosphorylate Themselves
Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate
Themselves
Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate
Themselves
Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate
Themselves
Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate
Themselves
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Phosphorylated Tyrosines on RTKs Serve as
Docking Sites for Intracellular Signaling Proteins
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Proteins with SH2 Domains Bind to
Phosphorylated Tyrosines
Proteins with SH2 Domains Bind to Phosphorylated Tyrosines
Proteins with SH2 Domains Bind to Phosphorylated Tyrosines
Proteins with SH2 Domains Bind to Phosphorylated Tyrosines
Proteins with SH2 Domains Bind to Phosphorylated Tyrosines
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• The GTPase Ras Mediates Signaling by Most RTKs
The GTPase Ras Mediates Signaling by Most RTKs
The GTPase Ras Mediates Signaling by Most RTKs
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Ras Activates a MAP Kinase Signaling Module
Ras Activates a MAP Kinase Signaling Module
Ras Activates a MAP Kinase Signaling Module
Ras Activates a MAP Kinase Signaling Module
Ras Activates a MAP Kinase Signaling Module
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Scaffold Proteins Help Prevent Cross-talk Between
Parallel MAP Kinase Modules
Scaffold Proteins Help Prevent Cross-talk Between Parallel MAP
Kinase Modules
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Rho Family GTPases Functionally Couple CellSurface Receptors to the Cytoskeleton
Rho Family GTPases Functionally Couple Cell-Surface Receptors to
the Cytoskeleton
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• PI 3-Kinase Produces Lipid Docking Sites in the
Plasma Membrane
PI 3-Kinase Produces Lipid Docking Sites in the Plasma Membrane
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• The PI-3-Kinase–Akt Signaling Pathway Stimulates
Animal Cells to Survive and Grow
The PI-3-Kinase–Akt Signaling Pathway Stimulates Animal Cells to
Survive and Grow
The PI-3-Kinase–Akt Signaling Pathway Stimulates Animal Cells to
Survive and Grow
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• RTKs and GPCRs Activate Overlapping Signaling
Pathways
RTKs and GPCRs Activate Overlapping Signaling Pathways
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Some Enzyme-Coupled Receptors Associate with
Cytoplasmic Tyrosine Kinases
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Cytokine Receptors Activate the JAK–STAT
Signaling Pathway
Cytokine Receptors Activate the JAK–STAT Signaling Pathway
Cytokine Receptors Activate the JAK–STAT Signaling Pathway
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Protein Tyrosine Phosphatases Reverse Tyrosine
Phosphorylations
SIGNALING THROUGH ENZYMECOUPLED RECEPTORS
• Signal Proteins of the TGFβ Superfamily Act
Through Receptor Serine/Threonine Kinases and
Smads
Signal Proteins of the TGFβ Superfamily Act Through Receptor
Serine/Threonine Kinases and Smads
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• The Receptor Notch Is a Latent Transcription
Regulatory Protein
The Receptor Notch Is a Latent Transcription Regulatory Protein
The Receptor Notch Is a Latent Transcription Regulatory Protein
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• Wnt Proteins Bind to Frizzled Receptors and Inhibit
the Degradation of β-Catenin
Wnt Proteins Bind to Frizzled Receptors and Inhibit the Degradation
of β-Catenin
Wnt Proteins Bind to Frizzled Receptors and Inhibit the Degradation
of β-Catenin
Wnt Proteins Bind to Frizzled Receptors and Inhibit the Degradation
of β-Catenin
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• Hedgehog Proteins Bind to Patched, Relieving Its
Inhibition of Smoothened
Hedgehog Proteins Bind to Patched, Relieving Its Inhibition of
Smoothened
Hedgehog Proteins Bind to Patched, Relieving Its Inhibition of
Smoothened
Hedgehog Proteins Bind to Patched, Relieving Its Inhibition of
Smoothened
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• Many Stressful and Inflammatory Stimuli Act
Through an NFκB-Dependent Signaling Pathway
Many Stressful and Inflammatory Stimuli Act Through an NFκBDependent Signaling Pathway
Many Stressful and Inflammatory Stimuli Act Through an NFκBDependent Signaling Pathway
Many Stressful and Inflammatory Stimuli Act Through an NFκBDependent Signaling Pathway
Many Stressful and Inflammatory Stimuli Act Through an NFκBDependent Signaling Pathway
Many Stressful and Inflammatory Stimuli Act Through an NFκBDependent Signaling Pathway
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• Nuclear Receptors Are Ligand-Modulated
Transcription Regulators
Nuclear Receptors Are Ligand-Modulated Transcription Regulators
Nuclear Receptors Are Ligand-Modulated Transcription Regulators
Nuclear Receptors Are Ligand-Modulated Transcription Regulators
Nuclear Receptors Are Ligand-Modulated Transcription Regulators
Nuclear Receptors Are Ligand-Modulated Transcription Regulators
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• Circadian Clocks Contain Negative Feedback Loops
That Control Gene Expression
Circadian Clocks Contain Negative Feedback Loops That Control Gene
Expression
ALTERNATIVE SIGNALING ROUTES
IN GENE REGULATION
• Three Proteins in a Test Tube Can Reconstitute a
Cyanobacterial Circadian Clock
Three Proteins in a Test Tube Can Reconstitute a Cyanobacterial
Circadian Clock
Three Proteins in a Test Tube Can Reconstitute a Cyanobacterial
Circadian Clock
Three Proteins in a Test Tube Can Reconstitute a Cyanobacterial
Circadian Clock
Three Proteins in a Test Tube Can Reconstitute a Cyanobacterial
Circadian Clock