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