Signal Transduction

Signal Transduction 1 Objectives: • • • • • Define first messenger (Hormones) List hormone types Describe receptor types Outline the hormone receptors interactions Describe second messenger mechanism of action • List second messengers 3 4/27/06 Signaling Overview 1. Introduction A. Definitions B. Components involved in signaling C. Types of signaling 2. Types of Signaling Ligands - cell-surface vs. intracellular 3. Three Major Classes of Signaling Receptors Ion Channel-linked G protein-coupled receptors (GPRs) Enzyme-linked receptors Tyrosine-Kinase Receptors Overview Mechanism of activation Different ways that TKRs can be activated TKs that are non-covalently linked with receptors 4. Second Messengers: cAMP, cGMP, IP3 and DAG, Ca+2, PIP3 5. Signaling Cascades A. Ras GTPase B. Adaptor proteins with SH2 and SH3 domains C. MAP kinase pathway D. 5 different kinases activated by different cascades E. JAK-STAT pathway 4 Signaling Overview 1. Introduction A. Definitions Signaling: Cell-cell communication via signals. Signal transduction: Process of converting extracellular signals into intra-cellular responses. Ligand: The signaling molecule. Receptors: Bind specific ligands. Transmit signals to intracellular targets. Different receptors can respond differently to the same ligand. B. Components involved in signaling: Ligands Receptors Intracellular Signaling Proteins Intermediary Proteins Enzymes Second Messengers Target Proteins Inactivating Proteins 5 Overview of Signal Transduction Signaling is responsible for how cells can respond to their environment and how they can differentiate or change over time Signals get translated into cellular responses or changes in gene expression Not all of the receptor needs to be bound to induce a response Signals can act locally or at a distance Responses can be fast or slow Signals are amplified Signaling Overview 1. Introduction C. Types of signaling i. Contact-dependent - via proteins in the PM: ii. Via Secreted Signals: a. Autocrine - via growth factors, cell that releases the signal is also the target. b. Paracrine - via neurotransmitters and cytokines, action on adjacent target cells. c. Endocrine - via hormones, action on distant target cells. d. Synaptic - via neurotransmitters, action on post-synaptic cell in response to electrical stimuli 2. Types of Signaling Ligands: A. Ligands that bind to cell-surface receptors: 1. Neurotransmitters (NT), i.e. norepinephrine, histamine hydrophilic (charged, polar) 2. Peptide hormones (P), i.e. insulin - can't cross membrane 3. Growth factors (GF), i.e. NGF, EGF, PDGF 4. Lipophilic signaling molecules, i.e. prostaglandins B. Ligands that bind to intracellular receptors: lipid soluble hormones that diffuse across the plasma membrane and interact with receptors in the cytosol or nucleus. i.e. steroids, thyroxine, retinoic acid, nitric oxide. 12 Types of Signaling Local vs. Circulating hormones 13 4/27/06 Chemical classes of hormones  Lipid-soluble hormones- use transport proteins in the plasma Steroid: Lipids derived from cholesterol. –Are lipophilic hormones. Testosterone. Estradiol. Cortisol. Progesterone. Thyroid ( amine but lipid soluble) Nitric oxide (NO) 14 University of Jordan Chemical classes of hormones  Water-soluble – circulate in “free” form in the plasma • Amines: Hormones derived from tyrosine and tryptophan. • Polypeptides and proteins: Polypeptides: • Chains of < 100 amino acids in length. ADH. Protein hormones: • Polypeptide chains with > 100 amino acids. • Growth hormone. • Eicosanoid (prostaglandins) derived from arachidonic acid (20 carbon 4 double bonds) 15 University of Jordan Chemical Classification of Hormones • Glycoproteins: • Long polypeptides (>100) bound to 1 or more carbohydrate (CHO) groups. • FSH and LH, TSH and hCG (human chorionic gonadotropin) They have α and β subunits (α is common and β is specific) • Hormones can also be divided into: • Polar: • H20 soluble. • Nonpolar (lipophilic): • H20 insoluble. • Can gain entry into target cells. • Steroid hormones and T4 (thyrxine –tetraiodothyronine)) 16 University of Jordan