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Lecture 7

BIOL 2P03 Lecture 7: Week 7 Screencast - Signaling Pathways that Control Gene Expression

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Brock University
Mark K Lukewich

BIOL 2P03 Week 7 Screencast – Signaling Pathways that Control Gene Expression th th February 27 – March 5 , 2017 Signal Transduction • Produces meaningful changes in cell function or morphology via: – Modification of existing proteins • Short-term effects – Synthesis of new proteins • Long-term effects Gene Expression • Refers to the utilization of DNA to synthesize ‘gene products’ – Typically DNA is used to synthesize mRNA which is then used to produce a polypeptide or protein • The complement of proteins expressed by a particular cell determines its function – There are non-protein gene products that also exist • tRNA • snRNA Regulation of Gene Expression • Can occur at several steps of the gene expression pathway – Chromatin decondensation – Transcription initiation – Elongation – RNA processing – mRNA export from the nucleus – Translation Regulation of Transcription Initiation • RNA polymerase synthesizes RNA from genomic DNA – Binds to the promoter to initiate transcription • This process is regulated by transcription factors – Transcription factors can either activate or repress transcription • Bind to specific DNA sequences and affect ability of RNA polymerase to bind to promoter – Transcription of a single Eukaryotic gene is often regulated by multiple transcription factors Primary Mechanisms for Regulating Gene Expression 1. Receptor-associated kinases – Receptor either • possess intrinsic kinase activity – receptor tyrosine kinases • is tightly bound to a kinase – cytokine r eceptors – Receptor activation leads to activation of kinase which then phosphorylates target proteins Receptor Tyrosine Kinases • Plasma membrane receptors with intrinsic tyrosine kinase activity • Consist of: – Extracellular domain that binds to ligand – Transmembrane domain that embeds receptor in plasma membrane – Cytosolic tyrosine kinase domain • Tyrosine kinase activity at rest is very low • Binding of ligand to receptor causes conformational change that stimulates receptor dimerization • Brings kinases in close proximity – They begin to phosphorylate each other • Phosphorylation enhances activity of tyrosine kinase – Begins to phosphorylate target proteins also (not pictured) • Phosphorylation sites also serve as binding sites for phosphotyrosine binding proteins • Act as a scaffold Ras/MAP Kinase Pathway • Common signaling pathway downstream of receptor tyrosine kinase activation Ras • Small G-protein • Possesses a binding site for GDP/GTP and has an intrinsic GTPase • Switching of GDP with GTP activates Ras Ras/MAP Kinase Pathway Ras • Unlike heterotrimeric G-proteins, Ras cannot directly interact with receptors • Requires intermediate proteins to couple receptor activation to Ras activation – These intermediate proteins facilitate the exchange of GDP for GTP Ras/MAP Kinase Pathway • Ras bound to GTP activates a series of kinases ultimately leading to the phosphorylation of MAP
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