Outline

14.1 TGFp Receptors and the Direct Activation of Smads

14.2 Cytokine Receptors and the JAK-STAT Pathway

14.3 Receptor Tyrosine Kinases and Activation of Ras

14.4 MAP Kinase Pathways

14.5 Phosphoinositides as Signal Transducers

14.6 Pathways That Involve Signal-Induced Protein Cleavage

14.7 Down-Modulation of Receptor Signaling

TABLE 14-1 Overview of Major Receptor Classes and Signaling Pathways Receptor Class/Pathway Distinguishing Characteristics

Receptors Linked to Trimeric G Proteins

G protein-coupled receptors (13)

Ligands: Epinephrine, glucagon, serotonin, vasopressin, ACTH, adenosine, and many others (mammals); odorant molecules, light; mating factors (yeast) Receptors: Seven transmembrane a helices; cytosolic domain associated with a membrane-tethered trimeric G protein

Signal transduction: (1) Second-messenger pathways involving cAMP or IP3/DAG; (2) linked ion channels; (3) MAP kinase pathway

Receptors with Intrinsic or Associated Enzymatic Activity

TGFp receptors (14, 15)

Ligands: Transforming growth factor p superfamily (TGFp, BMPs), activin, inhibins (mammals); Dpp (Drosophila)

Receptors: intrinsic protein serine/threonine kinase activity in cytosolic domain (type i and II)

Signal transduction: Direct activation of cytosolic Smad transcription factors

Cytokine receptors (14, 15)

Ligands: Interferons, erythropoietin, growth hormone, some interleukins (IL-2, IL-4), other cytokines

Receptors: Single transmembrane a helix; conserved multi-p strand fold in extracellular domain; JAK kinase associated with intracellular domain Signal transduction: (1) Direct activation of cytosolic STAT transcription factors; (2) PI-3 kinase pathway; (3) IP3/DAG pathway; (4) Ras-MAP kinase pathway

Receptor tyrosine kinases (14)

Ligands: Insulin, epidermal growth factor (EGF), fibroblast growth factor (FGF), neurotrophins, other growth factors

Receptor: single transmembrane a helix; intrinsic protein tyrosine kinase activity in cytosolic domain

Signal transduction: (1) Ras-MAP kinase pathway; (2) IP3/DAG pathway; (3) PI-3 kinase pathway

Receptor guanylyl cyclases (13)

Ligands: Atrial natriuretic factor and related peptide hormones

Receptor: single transmembrane a helix; intrinsic guanylate cyclase activity in cytosolic domain

Signal transduction: Generation of cGMP

Receptor phosphotyrosine phosphatases

Ligands: Pleiotrophins, other protein hormones

Receptors: intrinsic phosphotyrosine phosphatase activity in cytosolic domain inhibited by ligand binding

Signal transduction: Hydrolysis of activating phosphotyrosine residue on cytosolic protein tyrosine kinases

T-cell receptors

Ligands: Small peptides associated with major histocompatability (MHC) proteins in the plasma membrane of macrophages and other antigen-presenting cells Receptors: Single transmembrane a helix; several protein kinases associated with cytosolic domain; found only on T lymphocytes

Signal transduction: (1) Activation of cytosolic protein tyrosine kinases; (2) PI-3 kinase pathway; (3) IP3/DAG pathway; (4) Ras-MAP kinase pathway

TABLE 14-1 Overview of Major Receptor Classes and Signaling Pathways

Receptor Class/Pathway

Distinguishing Characteristics

Receptors That Are Ion Channels

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