D103 LH lect18C

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

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Page 1 -cyclic nucleotides (cAMP, cGMP) inorganic ion (Ca 2+ ) -   widely used - 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
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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 ? GTPases are a large family of hydrolase enzymes that can bind and hydrolyze GTP.  They are 
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D103 LH lect18C - Second Messengers -cyclic nucleotides...

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