D103 LH lect18C

D103 LH lect18C - Second Messengers -cyclic nucleotides...

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Page 1 -cyclic nucleotides (cAMP, cGMP) - inorganic ion (Ca 2+ ) -widelyused - triggers many different events (e.g. muscle contraction, exocytosis, activation of T cells and B cells, etc.) - stored in ER, mitochondrial, vesicles, extracellular fluid . - hydrophobic lipids (diacylglycerol; DAG) - phosphoinositols (inositol (1,4,5) trisphosphate; IP3) - dissolved gas (nitric oxide, NO) Second Messengers
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Page 2 Formation of phosphoinositides via phosphorylation of phophoinositol by phosphoinositol kinases Note - several different phospholipases (e.g. - C , - D , - A 2 ) can cleave PIP 2 at different locations to generate substrates for additional signaling pathways. Lipid kinases and lipid phosphatases also function to generate a wide range of signaling molecules.
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Page 3 IP 3 mediates release of intracellular Ca 2+ from endoplasmic reticulum, which functions with DAG to activate PKC Ca 2+ binds to PKC. Ca 2+ -bound PKC binds to DAG. PKC becomes active, and phosphorylates a wide range of target proteins. vertebrates have > 10 different PI-PLC's ! - enables tissue-specific coupling of various receptors to production of IP 3 and DAG. vertebrates have > 10 different PKC's ! - provides a selective response to various lipid second messengers
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Page 4 Lecture 18 – Signaling III - Trimeric Guanosine triphosphate binding-protein (G-protein) coupled seven transmembrane α -helix receptors a seven α -helix ‘serpentine’ transmembrane receptor a trimeric G- protein Recommended reading: MBOC 5e, p904-921 (G-protein coupled receptors)
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Page 5 GPCR are 7-transmembrane receptors that use heterotrimeric G-proteins to relay signals from the receptor to membrane-linked enzymes or ion channels. GPCR mediate response to a wide range of stimuli including hormones and neurotransmitters; ligands include proteins, small peptides, amino acids derivatives and fatty acids. GPCR constitute the largest family of cell surface receptors and are found in all eukaryotes. 5 % of genes in C.elegans are GPCR; many thousands of genes in mammals are GPCR (over 1000 genes alone involved in olfaction). The same ligand can activate multiple different receptor types e.g. - adrenaline activates 9 receptors. • All liganded 7-TM receptors stimulate the G protein’s α subunit to exchange bound GDP for cytosolic GTP . Basic facts about G protein coupled receptors (GPCR)
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Page 6 • Participate in many cellular activities : - Membrane traffic - Nuclear transport - Signal transduction - Regulation of the cytoskeleton - Protein synthesis - Protein translocation in ER What are GTPases ?
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D103 LH lect18C - Second Messengers -cyclic nucleotides...

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