D103 LH lect19_C

D103 LH lect19_C - Lecture 19 Signaling IV Cell Surface...

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Page 1 Lecture 19 – Signaling IV Cell Surface Receptors with Intrinsic or Associated Enzyme Activity stimulus receptor transduction effector Enzyme-linked cell surface receptors were originally identified based on their ability to stimulate growth, proliferation, differentiation or survival of cells upon exposure of the cells to extracellular proteins known as “growth factors”. Growth factors are present at low levels (in general 10 -9 -10 -11 M) Following exposure to growth factors, cells can respond both rapidly (e.g. changes in the cytoskeleton within minutes) and slowly (e.g. induction of target gene expression that can take hours). Disorders in signaling by enzyme-linked cell surface receptors and components of their pathways is an important cause of developmental defects and cancer . Reading: MBOC5e, p921-945
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Page 2 As with GPCR, enzyme-linked cell surface receptors are transmembrane proteins , with a ligand-binding domain on the outside of the cell. Unlike GPCR, enzyme-linked cell surface receptors are usually single-pass transmembrane proteins. In contrast to GPCR, the cytoplasmic domain of enzyme-linked receptors does not associate with a trimeric G-protein. The cytoplasmic domain of an enzyme-linked cell surface receptor can have intrinsic enzyme activity , or may be physically associated with an enzyme. The Enzyme is often a kinase (or phosphatase ) with specificity for a tyrosine, serine or threonine amino acid. Enzyme-linked cell-surface receptors GPCR ‘Enzyme-linked’
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Page 3 Receptor tyrosine kinases -have intrinsic kinase activity; phosphorylate specific tyrosine (Y) residues on a small set of intracellular signaling proteins. Tyrosine-kinase associated receptors - these cell surface receptors don't have intrinsic kinase activity, but instead they associate with proteins that have such activity. Receptor serine / threonine kinases -have intrinsic kinase activity; phosphorylate specific serine (S) or threonine (T) residues on intracellular signaling proteins. ‘Receptor-like’ tyrosine phosphatases - remove phosphate groups from tyrosines. Termed ‘receptor-like’ because no ligand has to date been found for these proteins. Receptor guanylyl cyclases - directly catalyze synthesis of cGMP in cytosol. There are five major classes of enzyme-linked cell surface receptors
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Page 4 Single-pass TM receptors can be activated by different methods Many ligands cause cross-linking ( dimerization ) of receptors. The dimerized receptor subunits phosphorylate each other. In some cases, the receptor may exist as a dimer in the absence of ligand. However, the dimeric receptor needs to be bound by ligand before each subunit is activated (e.g. insulin receptor). Monomeric ligands can be concentrated
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D103 LH lect19_C - Lecture 19 Signaling IV Cell Surface...

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