G protein

E96e5a67f45b1d18dbdcfd9eb62f87fb?s=47 sms1371
December 19, 2012
26

G protein

Guanine Nucleotide-Binding Protein

E96e5a67f45b1d18dbdcfd9eb62f87fb?s=128

sms1371

December 19, 2012
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    Guanine Nucleotide-Binding Protein G Protein Presented by Dr Sadatinejad, Seyyed

    Mohsen,student of Medicine from Iran,Kashan 19/12/2012
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    • Large G-Proteins (Heterotrimeric G Proteins) • In G protein-coupled

    receptors (GPCR) • 3 Subunits : α, β, γ • Small G-Proteins (Momomeric G Protein) • Subunit : α
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    GPCR or GPLR (G protein coupled receptors) (G protein linked

    receptors) • seven-transmembrane domain receptors (7TM receptors) • heptahelical receptors • serpentine receptor
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     Binding ligand  Changing conformation of GPCR  Acting

    GPCR as GEF (guanine nucleotide exchange factor )
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     Exchanging GDP for a GTP (inside the cell) &

    Activating G protein  Dissociating the subunit α binding GTP from β & γ subunits
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     Affecting subunit α to intracellular signaling proteins(Effect Protein) or

    target functional proteins directly (finally a cascade) depending on the α subunit type
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    Pathways :  Changing Polarization of membrane by Activating or

    Inactivating chanells.  cAMP  IP3 & DAG
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    Types of α subunit : • Gi/o • Gz (αi

    , αo ) (αz ) Inhibition of Adenylate Cyclase Change K+-channels gating Change Ca2+-channels gating Inhibition of Adenylate Cyclase & Activation of phosphodiesterase (PDE)
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    Types of α subunit : • Gi/o (αi , αo

    ) Inhibition of Adenylate Cyclase Change K+-channels gating Change Ca2+-channels gating
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    Some example of these receptors : • NEP ( α2

    receptor) • Somatostatin (GHRIH) • PIH (Prolactin Inhibiting H.) • Histamin (H3,H4 Receptor) • Acetylcholine M2 & M4 receptors • Dopamine D2, D3, D4 receptors • GABA receptors • Prostaglandin receptors • Serotonin receptors
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    Types of α subunit : • Gz (αz ) Inhibition

    of Adenylate Cyclase & Activation of phosphodiesterase (PDE)
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    Types of α subunit : • Gs • Golf •

    Gt • Ggust (αstimulatory ) (αolfactory ) (αtransdusin ) (αgastdusin ) Activation of Adenylate Cyclase
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    Some example of these receptors : • Glucagon • ADH

    (Kidney receptor) • LH & FSH • Histamin (H2 Receptor) • NEP (B1-Adrenergic receptor) • CRH (Corticotropin(ACTH) RH receptors) • ACTH receptors • GHRH • Dopamine receptors (D1 & D5) • Calcitonin receptors • Secretin receptors • Thyrotropin (TSH) receptors • Prostaglandin receptors • Prostacyclin receptors • Parathyroid (PTH) receptors • Melanocortin receptors
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    protein kinase A (PKA) Phosphorilation ADH : Promotes water retention

    by the kidneys GHRH & GHRIH : Stimulates & inhibits the synthesis and release of GH CRH : Stimulates the synthesis and release of ACTH ACTH : Stimulates the synthesis and release of Cortisol TSH : Stimulates the synthesis and release of a majorityof T4 Glucagon : Stimulates glycogen breakdown LH & FSH : Stimulates follicular maturation and ovulation Calcitonin : Decreases blood calcium levels PTH & Calcitonin : Increasing & Decreases blood calcium levels Glucagon : Stimulates lipogenesis Glucagon : Stimulates Insulin synthesis
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    Types of α subunit : • Go • Gt •

    Ggust (αolfactory ) (αtransdusin ) (αgastdusin ) Activation of AC
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    Types of α subunit : • Gq • G12/13 (αq

    , α11 , α14 , α15 , α16 ) (α12 , α13 ) Activation of PhosphoLipase C (PLC) Activation of Rho family of GTPases
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    Some example of these receptors : • NEP ( α1

    receptor) • TRH receptors • GnRH receptors • Vasopressin (ADH in all organ except kidney receptors) • Histamin (H1 receptor) • Acetylcholine M1, M3, M5 muscarinic receptors • Angiotensin II receptor (type 1) • Calcitonin receptor
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    Gq ► Effector protein : Phospholipase C (PLC) Cleavege membrane

    Phosphoinositol (PIP2 ) DAG IP3 Activation of protein kinase C Release of intracellular Ca2+ Regulation of other enzymes (by protein phosphorylation) Regulation of other enzymes (by Ca2+) Vasopressin (ADH) : Induces vasoconstriction TSH : Induces the synthesis and release of a small amount of T4 Angiotensin II : Induces Aldosterone synthesis and release TRH : Induces the synthesis and release of TSH GnRH : Induces the synthesis and release of FSH and LH
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    G12/13 ► Effector protein : Rho Protein (specially in Fibroblasts)

    Activating Rho protein Various action e.g. : • Polimerization microtubule & microfilament (Actin) • Remoding Sytoskeleton & Changing cell shape (& regulating cell migration, phagocytosis,…) • Function in cell cycle (mitosis & cytokinesis) • Controling cell polarity • Vesicular trafficking • Apoptosis • Wound healing ▼
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    G βγ (Beta-gamma complex) • Inhibition of the Gα subunit

    • Activate G protein coupled Inward-Rectifying Potassium Channels (Kir , GIRK) • Activation of PLA2 when bound to histamine receptors • Activating PLC, as a minor mechanism of GHRH • Activation L-type calcium channels
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     -Inherent GTPase activity of G-protein Slow GTP hydrolasis capability

    of Gα associating Gβγ Allostrically Exchanging GTP/GDP  -Regulator of G protein signalling (RGS)  or GTPase-activating proteins (GAP)  -GAP activity of Effector (PLC or AC)
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    Small G Protein • Small protein (20-kDa to 25-kDa) •

    binding to guanosine triphosphate (GTP) = activation • homologous to Ras GTPases (also called the Ras superfamily GTPases)
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    • Regulating metabolic enzymes • Regulating ion channels & transporters

    • Controlling transcription • Controlling motility & contractility • Controlling secretion • Systemic Regulating : • Embryonic development • Learning and memory • homeostasis
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    • Diabetes • Blindness • Allergies • Depression • Cardiovascular

    defects • certain forms of Cancer • In some disease Like : Cholera