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SL+D103+lecture+10+Signaling+V - D103: Cell Biology Dr....

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D103: Cell Biology Dr. Shin Lin
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Lecture 9 Signaling V Cell Surface Receptors with Kinase activity Recommended Reading: MBOC, 5th edition, p.921-945
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Page 3 1. General background on cell surface receptors with intrinsic or associated enzyme activity. 2. Examples of different ways in which cell surface receptors can be activated. 3. Illustration of principles - three different classes of cell surface receptors that have either intrinsic or associated kinase activity, plus their downstream effectors : Receptor Transduction signaling proteins Receptor tyrosine kinase Ras / MAP kinase TGF b -family receptors Smads Cytokine receptors JAK's / STAT's 4. Examples of diseases associated with defects in these pathways. D103 Fall 2011 Lecture 10 © Lin All rights reserved
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Page 4 Cell Surface Receptors with Intrinsic or Associated Enzyme Activity Enzyme-linked cell surface receptors are transmembrane proteins, with ligand-binding domains on the outer surface of the cell. Enzyme-linked cell surface receptors are usually single-pass transmembrane proteins, unlike G- protein-linked receptors with 7 transmembrane segments. The cytoplasmic domain of an enzyme-linked cell surface receptor can have either intrinsic enzyme activity, or may be directly associated with an enzyme. The enzyme is often a kinase (or phosphatase) with specificity for a tyrosine, serine or threonine amino acid. D103 Fall 2011 Lecture 10 © Lin All rights reserved
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Page 5 Enzyme-linked cell surface receptors were originally identified by their ability to stimulate growth, proliferation, differentiation or survival of cells exposed to extracellular signal molecules known as “ growth factors ”. Growth factors act at very low concentrations (10 -9 - 10 -11 M), by binding to the cell surface receptors with high affinity. Following exposure to growth factors, cells can respond both rapidly (e.g. changes in the cytoskeleton within minutes) and slowly (e.g. induction of gene expression that can take hours). Abnormalities of signaling through enzyme-linked cell surface receptors have major roles in developmental defects and diseases such as cancer . D103 Fall 2011 Lecture 9 © Lin All rights reserved
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Page 6 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
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SL+D103+lecture+10+Signaling+V - D103: Cell Biology Dr....

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