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1、13 Biosignaling,13.1 Concept of biosignaling 13.2 Features of biosignaling 13.3 Four major pathways,Important roles of biosignaling,functional integration of distant organs, tissues and cells requires communication; Signaling is perhaps a primal requirement to respond to our environment; The foundat

2、ion of any complex response pathway lies with cellular biochemicals.,Four schemes of intercellular signaling (1),Four schemes of intercellular signaling (2),13 Biosignaling,13.1 Concept of biosignaling 13.2 Features of biosignaling 13.3 Four major pathways,Features (1),Scatchard analysis quantifies

3、the receptor-ligand interaction,Ka : association constant; Kd : dissociation constant,Scatchard analysis quantifies the receptor-ligand interaction,often short-lived G proteins are integral membrane protein, hetertrimers (); G proteins have similar and subunits, but differ in the type of -subunits;

4、When G-protein is activated, the subunit dissociates to interact with an enzymes that generate second messengers (e.g. cAMP).,G protein (2),G protein (3, - subunits),G protein (3, mechanism),The Nobel Prize in Physiology and Medicine 1994,Alfred G. Gilman,Martin Rodbell,USA,USA,1941-,1925-1998,for t

5、heir discovery of G-proteins and the role of these proteins in signal transduction in cells,synthesized in adrenal medulla; belongs to catecholamines; target cells include liver, skeletal muscle, heart muscle and adipose; released in response to acute stress “fight or fight response”,Epinephrine sig

6、nal (1),Epinephrine signal (2, process),Self-Inactivation of Gs,Epinephrine signal (3),Epinephrine signal (4, cAMP),Epinephrine signal (5),cAMP acts as a second messenger,Activation of cAMP-dependent protein kinase, PKA,Epinephrine signal (6),Epinephrine Cascade,Epinephrine signal (7),Desensitization of the -adrenergic receptor in the continued presence of epinephrine,-adrenergic protein kinase (ARK) -arrestin (arr),prevents interaction between receptor and G protein,Epinephrine signal (8),cAMP cGMP Inosite1,4,5-triphosphate (IP3) Diacylglycerol Ca2+,Second Messengers,Phosphoinositide Casca

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