Signaling _Chap 15_ note - Signaling I(Lodish Chapter 15...

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Signaling I (Lodish Chapter 15; Lodish page 311-314) I. Introduction to signaling. Today we will talk about general concepts of signal transduction and one of the major signal transduction pathway: the G protein coupled signaling pathway. A. What is signaling: a ligand binds and activates a receptor which activated a cascade of signaling molecules and effectors, which finally cause cellular response. That is, a cell converts an extracellular signal into a response (Lodish Fig. - 15-1). B. Why is signaling important (Alberts Fig. 15-2). Important for cell communication. C. Eight signaling pathways (Lodish Fig. 16-1). II. Four goals A. Transduction of signal across the plasma membrane – we will focus on pathways where the signal cannot cross the PM. These pathways use either G-protein coupled receptors, enzyme linked or coupled receptors B. Generation of a secondary messenger in the cytoplasm – cAMP, inositol triphosphate (IP3) or Ca++ C. Secondary messenger influences effector molecule (protein kinase A, protein kinase C, MAPK and transcription factors). Pathways can and often do have several secondary messengers and effectors. D. To become familiar with the major signaling pathways (related to A). III. Modes of Signaling (Lodish Fig. 15-2) A. Endocrine – long range (e.g. steroid hormones, insulin, growth hormone): slow but last longer. B. Paracrine signaling – long range (1-25 cells). Epidermal growth factor C. Autocrine signaling D. Signaling by plasma-membrane attached proteins (contact-dependent) E. Additional modes: Synaptic signaling: fast and precise; Signal via gap junctions F. Two types of receptors: Cell surface receptors and intracellular (nuclear) receptors, letter of which are the receptors for the steroid hormones. IV. Nuclear receptor superfamily A. Small hydrophobic signaling molecules: steroid hormones, thyroid hormones (Lodish Fig. 7-46) B. Diffuse through the plasma membrane to the nucleus C. The nuclear receptors are normally transcription factors, each of which has at least a DNA binding domain and a ligand-binding domain (Lodish Fig. 7-47). D. When bound to the signaling molecules, the transcription factors regulate gene transcription (Lodish Fig. 7-50). 1. In the absence of hormone, the receptor is in a complex with inhibitor proteins in the cytosol, thus is inactive. 2. In the presence of hormone, the inhibitor is dissociated. 3. The receptor-ligand complex is translocated into the nucleus. 4. The DNA binding domain binds DNA and stimulates transcription of target genes. Signal transduction I 1
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V. Cell surface receptors A. Three major classes (Alberts Fig. 15-15) 1. Ion-channel coupled receptors: neurotransmission 2. G-protein coupled receptors: second messenger: cAMP 3. Enzyme-linked receptors: protein phosphorylation, proteolysis a. Serine/threonines kinases b. Tyrosine kinases B. A simple intracellular signaling pathway mediated by membrane receptors (Lodish Fig.
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