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Chapter 15 Notes (Summer2011)

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University of Toronto Scarborough
Biological Sciences
Rosada Silva

BIOB11Summer2011 Chapter 15 Cell Signalling and Signal Transduction Basic Elementso Cells usually communicate via extracellular messenger moleculeso 3 types distances autocrine paracrine and endocrineo Autocrine released from the cell and taken up by the same cell through receptors o Paracrine released from a cell and taken up by another cell through receptors o Endocrine hormone released travels and is taken up by another cell at another location farther through receptorsOverview of Major Signaling Pathways by which Extracellular Messenger Molecules can elicit Intracellular Responses o Initiationrelease of a messenger molecule o Only cells expressing a receptor for that molecule can respondsignal is transmitted not molecule once the molecule attaches to the receptor o 2 modes of signal transmission once the signal reaches the cytoplasmic domain through a second messenger or by recruiting proteins o Through a second messenger receptor transmits a signal to cytoplasmic domaincytoplasmic domain transmits signal to nearby enzyme effector which generates a second messengersecond messenger may diffuse through cell or remain in the membraneo By recruiting proteins receptor transmits a signal to cytoplasmic domaincytoplasmic domain transforms into recruiting station for cellular signalling proteinspathway consists of a serioes of proteins that operate in sequencetypically each protein alters the conformation of the next proteins often protein kinases or phosphotases who add or remove phosphate groups Extracellular Messengers and Receptorso Large variety of extracellular messengers amino acids and their derivatives gases steroids derived from cholesterol eicosanoidsnon polar molecules derived from fatty acids polypeptides and proteinso Usually extracellular signalling molecules are recognized by specific receptors on surface of signal receiving cello Receptors G protein coupled receptors GPCRsactivate GTPbinding proteins G proteins receptor proteintyrosine kinases RTKs ligand gated channels steroid hormone receptors unique receptorsB and T cell receptorsG protein Coupled Receptorso Interact with G proteins o Also known as seventransmembrane receptors 7TMthey contain several transmembrane helices o Numerous diverse natural ligands hormones neurotransmitters chemoattractants odorants tastants photons o When bound to their ligand the receptor interacts with a trimeric G protein which activates an effectoro The alpha and gamma units of the G protein are linked to the membrane by lipid groups embedded in the lipid bilayer o 3 loops on the outside of the 7TM form the ligand binding site o GPCRs normally have amino terminus on outside of the cell seven alpha helices which are connected by loops of varying rdlength G proteins bind to the 3 intracellular loop and carboxy terminus on inside of the cello Numerous proteins can also bind to C terminuslink receptors to signalling proteins and effectorsG Proteinso Heterotrimerico Binds guanine nucleotidesGDP or GTP binds to the alpha subunit o Held at plasma membrane by lipid chainscovalently attached to the alpha and gamma subunits The Mechanism of Receptor Mediated Activation of Effectors by Means of G proteinso Receptor bound by extracellular ligand changes conformation of the intracellular domaincan now bind G proteins
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