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| Question | Answer |
| Example of ligands | • Small ions: ferric ion • Organic molecules: adrenalin • Polysaccharides: heparin • Peptides: insulin • Proteins: vascular endothelial growth factor |
| Signal transduction pathways | Signal transduction pathways convert extracellular stimuli into specific cellular responses (Campbell and Reece, 2004). Typically, signal transduction begins with a signal to a receptor and ends with a change in cell function. Sometimes the signal can be amplified, so a small signal can result in a large response |
| cell signaling steps | 1. signal reception 2. transduction pathway 3. response |
| TYPES OF EXTRACELLULAR SIGNALING SI | Endocrine, paracrine, synaptic, contact-dependent |
| Cell surface receptors vs intracellular receptors | Cell surface receptors: large, hydrophilic molecules Intracellular receptors: small hydrophobic molecule that can cross the membrane (tex steroid hormones) |
| GEF and GAP | Two regulatory proteins (can swith enzymes on and off) GEF = guanine nucleotide exchange factors: exchange of GDP to GTP GAP: GTP-activating proteins: switch off by GTP hydrolysis |
| 3 main classes of cell-surface receptors | ion channels coupled receptors: Transduction of chemical signal into an electrical signal i.e. voltage change across the plasma membrane G-protein coupled receptors: 7-pass transmembrane helices, the G protein has 3 subunits. Signal molecule binds the GPCR => activate G-protein that lose GDP affinity and exchange to GTP enzyme coupled receptors |
| alfa subunit of G-protein | Has intrinsic GTP-ase activity: Switches itself off by hydrolysing its bound GTP to GDP Linked to membrane by lipid tail |
| G-proteins interact with... | ...ion channels: immediate change of the cell status and behaviour ...enzymes: slower and more complex → additional intracellular signalling molecules, second messengers such as cAMP, IP3, DAG, Ca2+ |
| Enzyme-coupled receptors | Upon binding of signal (often local mediators such as growth factors), the receptor usually converts from an inactive monomeric state to an active dimeric state Largest class of enzyme-coupled receptors: receptor tyrosine kinase (RTK) has a tyrosine protein kinase function in cytoplasmic domain |
| Receptor tyrosine kinase (RTK) | 1. RTK forms a dimer in active state + phosphorylation on specific tyrosine of the kinase domains 2. Phosphorylated tyrosines will bind (many) intracellular signalling proteins with specialized interaction domains → signal transmission (biochemical changes) 3. Response ending by protein tyrosine phosphatases (removing phosphates on tyrosine of RTK) or destroyed in lysosomes |
| RAS | a key member of intracellular signalling proteins • small GTP-binding protein = monomeric GTPase • mutation in RAS genes is most common oncogen |
| MAP | mitogen-activated protein |
| Mitogen | chemical substance that triggers the cell to start cell division (mitogenesis) |
| Responses by acetylcholine in heart pacemaker cell, salivary gland cell and skeletal muscle cell | decreased heart rate of firing Secretion Contraction |
| Fast vs slow pathway | fast: Alters proteins function Slow: Changes in gene expression witch alters protein synthesis |
| Steroid hormones | For instance cortisol Are soluable in plasma membrane and can enter the cytosol and bind to an intracellular receptor in the cytosol or nucleas called nuclear receptors |
| Nuclear receptor | can work as a transcription factor once a hormone binds to it |
| signaling by GTP-binding proteins | - Trimeric G-proteins - monomeric GTPases Dont really know the difference... |
| Exampels of signalling by protein phophorylation | serine/threonine kinase and tyrosine kinase |
| Dephosphorylation happens by... | protein phosphatase |
| Gamma subunit | Linked to membrane with lipid tail |
| Cholera | activates alfa subunit G-protein and locking it with continuous adenylate cyclase stimulation and increase cAMP => increased cl- and water efflux => diarrheoa and dehydration |
| cell responses mediated by adrenaline | heart cells: increased heart rate skeletal cells: glycogen breakdown adipose tissue: fat breakdown |
| Ca2+ canntrigger... | ...egg cell development ...muscle contraction ...ca2+ responsive proteins |
| Example of a ca2+ responsive protein | calmodulin dependent protein kinases |
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