BCHE 395-18 2014 Biosignaling II

Conformagonal changes auer camp binding causes

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Unformatted text preview: Coupled Receptors β- Adrenergic Receptor System •  G- protein (αβγ) heterotrimer: receptor acGvated by hormone, GDP replaced by GTP and GSα in acGvated and separates –  GSα s6mulatory G protein, turned on and binds to Adenylyl cyclase (palmitoyl covalent aDachment) •  Adenylyl cyclase: integral membrane protein, acGve site in cytoplasm –  When sGmulated, catalyzes cAMP synthesis from ATP Prototypical G- protein: Ras •  Binds nucleo6de GTP •  Ala146 gives specificity to GTP over ATP •  Binding of GTP causes conformaGonal change, exposing “Switch” regions •  Switch regions interact with downstream proteins in the signaling pathway NOT heterotrimer Just Gs type Synthesis of cAMP •  cAMP is a secondary messenger –  Allosterically acGvates cAMP- dependent protein kinase A (PKA) –  PKA acGvaGon leads to acGvaGon of enzymes that produce glucose from glycogen Protein Kinase A •  cAMP acGvates cAMP- dependent Protein Kinase A (PKA) •  ConformaGonal changes aUer cAMP binding causes dissociaGon of C subunits •  Displacement of autoinhibitory domains (R subunit) •  Now acGve protein kinase à༎ •  Phosphorylates downstream enzymes and proteins AKAP A kinase anchoring protein PhosphorylaGon by PKA Serine and Threonine PhosphorylaGon by PKA Ex. Control of Glycogen Breakdown •  Epinephrine (& glucagon) signaling pathway •  Starts phosphoryla6on cascade via cAMP •  AcGvates enzyme glycogen phosphorylase –  Phosphorylates Serine14 •  Glycogen phosphorylase cleaves glucose residues off glycogen, generaGng glucose- 1- phosphate Signal AmplificaGon in Epinephrine Cascade •  AcGvaGon of few GPCRs...
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