Presented by Dr Sadatinejad, Seyyed Mohsen,student of Medicine from Iran,Kashan 2012
Presented by Dr Sadatinejad, Seyyed Mohsen,student of Medicine from Iran,Kashan 2012
Guanine Nucleotide-Binding Protein
G Protein
SIGNAL TRANSDUCTIONIon Channel Linked ReceptorEnzye Linked ReceptorG-Protein Coupled Receptor
G protein• GTP linking → Active• GDP linking → Inactive
Types of G-Protein in signal transduction
• 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
GPCR or GPLR(G protein coupled receptors) (G protein linked receptors)• seven-transmembrane domain receptors
(7TM receptors)• heptahelical receptors• serpentine receptor
Signal transduction pathwayBinding ligand Changing conformation of GPCRActing GPCR as GEF (guanine nucleotide
exchange factor )
Signal transduction pathwayExchanging GDP for a GTP (inside the
cell) & Activating G proteinDissociating the subunit α binding GTP from β
& γ subunits
Signal transduction pathwayAffecting subunit α to intracellular
signaling proteins(Effect Protein) or target functional proteins directly (finally a cascade) depending on the α subunit type
Signal transduction pathwayPathways : Changing Polarization of membrane by
Activating or Inactivating chanells.cAMPIP3 & DAG
Types of α subunit : 1.Gi-family
• Gi/o
• Gz
(αi, αo)
(αz)
Inhibition of Adenylate CyclaseChange K+-channels gatingChange Ca2+-channels gating
Inhibition of Adenylate Cyclase& Activation of phosphodiesterase (PDE)
Types of α subunit : 1.Gi-family
• Gi/o (αi, αo)Inhibition of Adenylate CyclaseChange K+-channels gatingChange Ca2+-channels gating
Smooth muscle contraction, Depress neuronal activity
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
1.Gi-family
Types of α subunit : 1.Gi-family
• Gz (αz) Inhibition of Adenylate Cyclase & Activation of phosphodiesterase (PDE)
Maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluid
Types of α subunit :
2.Gs-family• Gs
• Golf
• Gt
• Ggust
(αstimulatory)(αolfactory)(αtransdusin)(αgastdusin)
Activation of Adenylate Cyclase
Types of α subunit :
2.Gs-family• Gs (αstimulatory) Activation of Adenylate Cyclase
Increase heart rate, Smooth muscle relaxation, stimulate neuronal activity
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
2.Gs-family
• Dopamine receptors (D1 & D5)• Calcitonin receptors• Secretin receptors• Thyrotropin (TSH) receptors• Prostaglandin receptors• Prostacyclin receptors• Parathyroid (PTH) receptors• Melanocortin receptors
Gi & Gs Family► cAMP : Second Messenger
protein kinase A (PKA)
Phosphorilation
ADH : Promotes water retention by the kidneys
GHRH & GHRIH : Stimulates & inhibits the synthesis and release of GHCRH : 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
Types of α subunit : 2.Gs-family
• Go
• Gt
• Ggust
(αolfactory)(αtransdusin)(αgastdusin)
Activation of AC
SmellVisionTaste
Types of α subunit :
3.Gq-family• Gq
• G12/13
(αq , α11 , α14 , α15 , α16 )
(α12, α13)
Activation of PhosphoLipase C (PLC)
Activation of Rho family of GTPases
4.G12/13-familySmooth muscle contraction, Ca2+ flux
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
Gq-family
Gq ► Effector protein : Phospholipase C (PLC)
Cleavege membrane Phosphoinositol (PIP2)
DAG IP3
Activation ofprotein 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
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
▼
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
Ligandlight-sensitive compounds (vision)Odors (olfactory substance)Taste (Gustducin substance)PheromonesHormonesNeurotransmittersetc.
TERMNATION -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)
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)
G PROTEIN FUNCTION• Regulating metabolic enzymes• Regulating ion channels & transporters• Controlling transcription• Controlling motility & contractility• Controlling secretion• Systemic Regulating :
• Embryonic development • Learning and memory• homeostasis
MALFUNCTION OF G PROTEIN IN GPCR [G PROTEIN-COUPLED RECEPTOR] SIGNALING PATHWAYS • Diabetes• Blindness• Allergies• Depression• Cardiovascular defects• certain forms of Cancer• In some disease Like : Cholera
Thank you
Product by :3yyed moh3n sadatinejad