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ODSC 6A
| Question | Answer |
|---|---|
| I. General Principles of Signaling | |
| Signal transduction | refers to the movement of signals from outside to inside |
| Involves | ligand/receptor interaction, phosphorylation, kinases, amplification |
| Ligand binds to | receptor, ligand gives off signal |
| General Idea | |
| Slide 4Ligan/receptor interaction | |
| Types of signaling | autocrine, paracrine, endocrine |
| 1. Autocrine | molecules act on themselves |
| Ex | IL 2 and ostepontin |
| 2. Paracrine | (proxy)act on cells nearby |
| 3. Endocrine | act on cells far away |
| Ex | hormones |
| 4. Synaptic signaling | neurotransmitter released at the nerve terminal |
| II. Different types of signaling molecules or ligands | |
| 1. Hormones: Cortisol, estradiol, glucagon, insulin, testosterone, thyroid hormone | |
| 2. Growth factors: EGF, PDGF, NGF, TGF | beta |
| 3. Local mediators: Nitric oxide, Histamine | |
| 4. Extracellular matrix proteins: Collagen, Osteopontin, vitronectin, fibronectin | |
| 5. Neurotransmitters: Acetylcholine, g | Aminobutyric acid |
| Some molecules do NOT fit into one type ex | epinephrine which acts as hormone and neurotransmitter |
| III. How receptors relay signals via intracellular signaling | |
| Cellular signaling cascade can follow a | complex path |
| Receptor/ligand interaction activates | intracellular proteins that amplify the signals |
| Steps involved in signal transduction | |
| 1. Ligand binds to receptor | |
| 2. Signal cascade transfers signals into cell | |
| 3. Cascade is continued by other intracellular molecules | |
| 4. Cascade triggers response ex; divide | |
| Amplification of cell survival(anti apoptotic) signal by phosphorylatino and activation of akt | |
| IV. Different classes of receptors | |
| Extracellular receptors | on surface of the cell |
| Intracellular receptors | inside the cell in cytoplasm ex, steroids |
| Categories of Cell surface receptors | |
| Types of Receptors | ion, growth factor, G protein, integrin, steroid |
| 1. Receptors with No tyrosine kinase activity | have No kinases so recruit other receptors that have kinase activity |
| 2. Receptor Tyrosine kinase | have tyrosine kinase activity |
| Activation induces | dimerization and autophosporylation which stimulates activity of intracellular kinases |
| 3. Receptor Serine/threonine kinase | Transforming growth factor |
| Intracellular receptors | steroid receptor |
| 1. Steroid receptor | can cross plasma membrane and bind to receptors in the cytoplasm or on the nuclease |
| V. Intracellular proteins that act as molecular switches | |
| Kinases mediate | protein phosphorylation |
| Phosphatases removes | the phosphate group by hydrolysis |
| Kinases and phosphatases act as | molecular switches |
| Phosphorylation | most common posttranslational modification and mediate protein dephosphorylation |
| Intrinsic enzymatic activity | all can autophosphorylate, ex tyrosine kinases, tryosine phosphatases, serine/threonine |
| VI. Role of second messengers in the intracellular signaling | |
| Secondary messenger refers to an | intracellular signaling molecule that is downstream from the receptor |
| Examples of second messengers | Camp, IP3, DAG, metabolites of arachidonic acid, nitric oxide |
| Best characterized second messengers is | cAMP (cyclic AMP) |
| G protein | largest family of cell surface receptors, secondary messenger (homodimer) |
| Structure | polypeptide snakes through membrane 7 times |
| Trimeric G proteins | disassemble to relay signals from G proteins |
| Integration of multiple pathways | |
| Synergestic | two individual signals both activate the same protein at two different sites |
| Converge | two individual signals phosphorylate two different proteins which signals for active protein |
| VII. Protein, Protein interactions and modular domain | |
| Interactions are | complex interactions between signaling proteins |
| Mediated by | modular domains |
| Modular domains | specific/unique amino acid sequence |
| Common modular domains | SH2 SH3 PH |
| Role of Modular domains | mediate interaction between receptor and signaling proteins and also between signaling proteins inside the cell |
| VIII. Kinases and possible therapeutic targets for cancer | |
| Fluorosis | hypomineralization of teeth alters kinase and phosphatase activity |
| Enzymes such as kinase and phosphoratase can be used as | drug targets for protein inhibitors |
| Bisphosphonates | drugs that prevent and treat cancer induced osteoporosis by inhibiting osteoclasts |