D103 - Lecture 19 - Signaling V.docx

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Department
Biological Sciences
Course
BIO SCI D103
Professor
Grant Mac Gregor
Semester
Winter

Description
A. Cell Surface Receptors w/ kinase a. Receptor tyrosine kinases b. Tyrosine-kinase associated receptors c. Receptor serine/threonine kinase B. Classes of Cell surface receptors a. Receptor tyrosine Kinase i. Intrinsic kinase ii. Tyr b. Tyrosine-kinase associated receptors i. Lacks intrinsic kinase activity ii. Associates with proteins with tyrosine kinase activity b. Receptor Ser/Thr Kinase i. Intrinsic Kinase ii. Ser/Thr B. Intrinsic or associated kinase activity a. Receptors can have built in kinase ability or associated ones B. Tyrosine-kinase associated receptors a. Cross phosphorylation of receptors B. Single-pass transmembrane receptor a. Ligand induces dimerization or causes a preformed dimer to undergo conformational change b. Increase concentration of ligand nearby i. Proteoglycan has sugar molecules that attracts and binds to ligands (Type II, RII) 1. Brings ligands near the receptors B. Transforming Growth Factor-beta family receptors a. Process i. Ligand binds to RII, RII's kinase is always on, RI comes closer to RII, RII phosphorylates RI, RI-P phosphorylates R-Smad at 3 ser, NLS is exposed on R-Smad, R-Smad bind to other R-Smads by MH2 domain and Phosphorylated Serines, Importin binds with R-Smad + co-Smad, Smad/importin complex enters the nucleus, Importin leave Smad, Smad forms a transcriptional complex b. RIII i. Proteoglycans that sequesters ligands b. Smads i. Transducing signaling proteins b. TGF-beta receptors i. Active complex has 4 molecules 1. 2 R2 a. Has contstanly active kinase ability 2. 2 R1 a. Normally inactive kinase, but binding to R2 activates it ii. R1 gets phosphorylated by R2 1. R-Smad binds to the R1 phosphorylated a. Regulatory Smad b. Interacts with Receptor ii. R-Smad 1. Has MH2 and MH1 a. MH2 is phosphorylated by R1 i. Exposing NLS 2. 3 serines get phosphorylated and reveals NLS ii. Co-Smad helps to form the heterotrimer of Smads 1. Not phosphorylated 2. R-Smad+Importin+Co-Smad B. Ski proteins a. Disurpts Smad complex and blocks gene expression b. Leads to HDAC - histone deacetylation c. Inhibits transcription of target molecules B. Inhibition of TGF-signaling a. Ignore SARA - scaffolding b. Smad7 recruits a phosphatase (PP1c) to the for receptor 1 c. Turns off receptor B. 3 Smas a. Regualtory Smads b. Co-Smads c. Inhibitory Smads B. Fibrodysplasia ossificans progressiva (FOP) a. Ectopic ossification b. Repairing soft tissue damage.. -> cells turn into bone B. Cytokine Receptor Pa
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