Chapter 6 - Chapter 6 Protein Kinase Receptor - In one...

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Protein Kinase Receptor - In one class of receptors, kinase domain is an intrinsic part of the receptor ligand binding dimerizes the receptor, activating the kinases, which phosphorylate each other activated kinases phosphorylate downstream substrates Phosphorylation – covalent attachement of a phosphate group Protein Kinase associated w/ receptor - Clustering activates - In another class of receptors, a kinase is noncovalently associated with the receptor ligand binding dimerizes the receptor, activating the associated kinases, which phosphorylate each other the activated kinases phosphorylate downstream substrates Kinds of Domains - SH2 – bind to phosphotyrosine. SH3 – proline. PH/PX – phosphoinositides. PDX – C termini of proteins Scaffolds and Adaptors - Unphosphorylated scaffold Activation of protein kinase results in phosphorylation of a scaffold the phosphorylated scaffold recruits signaling proteins that bind to it the adaptor Grb2 binds to the signaling protein SOS via its SH3 domain an activated receptor becomes tyrosine phosphorylated Grb2 binds to the phosphotyrosine via its SH2 domain, bringing SOS to the receptor Amplification - Amplification be kinase cascades signaling results in the release of the second messenger calcium calcium rapidly diffuses throughout the cell and induce conformational change in calmodulin Small G proteins - Bound to GTP = activated - In resting state, small G proteins bound to GDP signaling activates guanine- nucleotide exchange factors (GEF) to displace GDP from small G proteins and allow GTP to bind over time, the small G protein hydrolyzes GTP to GDP Lipid Rafts - Cholesterol rich, Enriched for signaling proteins - Proximity is very important in regulating these processes - Membrane rafts are specialized regions of the cell membrane enriched for saturated lipids and cholesterol. GPI-linked proteins and acylated proteins such as src-family kinases are found in lipid rafts o Lipid rafts are dynamic structures that can change size and protein content. Some proteins migrate into lipid rafts when they are oligomerized by binding ligand Turn it off!! -
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Chapter 6 - Chapter 6 Protein Kinase Receptor - In one...

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