Heterotrimeric G protein

"G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins. These proteins are activated by G protein-coupled receptors and are made up of alpha (α), beta (β) and gamma (γ) subunits,[1] the latter two referred to as the beta-gamma complex.

Contents

Alpha subunits

Gα subunits consist of two domains, the GTPase domain, and the alpha-helical domain. There exist at least 20 different Gα subunits, which are separated into four main families. This nomenclature is based on their sequence homologies:[2]

G-protein-family α-subunit Gene Signal transduction Use/Receptors (examples) Effects (examples)
Gi-family
Gi/o αi, αo GNAO1, GNAI1, GNAI2, GNAI3 Inhibition of adenylate cyclase, opens K+-channels (via β/γ subunits), closes Ca2+-channels Muscarinic M2 and M4, chemokine receptors, α2-Adrenoreceptors, Serotonin 5-HT1 receptors, Histamine H3 and H4, Dopamine D2-like receptors Smooth muscle contraction, depress neuronal activity
Gt αt (Transducin) GNAT1, GNAT2 Activation of phosphodiesterase 6 Rhodopsin Vision
Ggust αgust (Gustducin) GNAT3 Activation of phosphodiesterase 6 Taste receptors Taste
Gz αz GNAZ Inhibition of adenylate cyclase  ? Maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids.
Gs-family
Gs αs GNAS Activation of adenylate cyclase Beta-adrenoreceptors; Serotonin 5-HT4, 5-HT6 and 5-HT7; Dopamine D1-like receptors, Histamine H2 Increase heart rate, Smooth muscle relaxation, stimulate neuronal activity
Golf αolf GNAL Activation of adenylate cyclase olfactory receptors Smell
Gq-family
Gq αq, α11, α14, α15, α16 GNAQ, GNA11, GNA14, GNA15 Activation of phospholipase C α1-Adrenoreceptors, Histamine H1, Serotonin 5-HT2 receptors, Muscarinic M1 M3, and M5 Smooth muscle contraction, Ca2+ flux
G12/13-family
G12/13 α12, α13 GNA12,GNA13 Activation of the Rho family of GTPases Cytoskelatal functions, Smooth muscle contraction

Beta-gamma complex

Main article: Beta-gamma complex

The β and γ subunits are closely bound to one another and are referred to as the beta-gamma complex. Upon activation of the GPCR, the Gβγ complex is released from the Gα subunit after its GDP-GTP exchange.

Function

The free Gβγ complex can act as a signaling molecule itself, by activating other second messengers or by gating ion channels directly.

For example, the Gβγ complex, when bound to histamine receptors, can activate phospholipase A2. Gβγ complexes bound to muscarinic acetylcholine receptors, on the other hand, directly open G protein-coupled inward rectifying potassium channels (GIRKs). They can also activate L-type calcium channels, as in H3 receptor pharmacology.

References

  1. ^ Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H (2000). "Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes". DNA Res 7 (2): 111–20. doi:10.1093/dnares/7.2.111. PMID 10819326. 
  2. ^ Strathmann MP, Simon MI (1991). "G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits". Proc. Natl. Acad. Sci. U.S.A. 88 (13): 5582–6. doi:10.1073/pnas.88.13.5582. PMC 51921. PMID 1905812. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=51921. 

External links

3.6.1
3.6.2
3.6.3-4: ATPase
3.6.3
Cu++ (3.6.3.4)
Ca+ (3.6.3.8)
Na+/K+ (3.6.3.9)
ATP1A1 · ATP1A2 · ATP1A3 · ATP1A4 · ATP1B1 · ATP1B2 · ATP1B3 · ATP1B4
H+/K+ (3.6.3.10)
ATP4A
ATP8B1 · ATP10A · ATP11B · ATP12A · ATP13A2 · ATP13A3 ·
3.6.4
3.6.5: GTPase
3.6.5.1: Heterotrimeric G protein

Rho family of GTPases: Cdc42 (CDC42, TC10, TCL) • RhoUV (RhoU, RhoV) • Rac (Rac1, 2, 3, RhoG) • RhoBTB (1, 2) • RhoH • Rho (A, B, C) • Rnd (1, 2, 3) • RhoDF (RhoF, RhoD)

other: Ras (HRAS, KRAS, NRAS) · Rab (RAB23, RAB27) · Arf (ARF6, SAR1B, ARL13B, ARL6) · Ran · Rheb · Rap
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
MAP
see MAP kinase pathway
Calcium
G protein
Heterotrimeric
ARFs · Rabs · Ras (HRAS, KRAS, NRAS)
Cyclin
Lipid
Other protein kinase
Other phosphoprotein phosphatase

Serine/threonine: Protein phosphatase 2

Tyrosine: protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase • Sh2 domain-containing protein tyrosine phosphatase

both: Dual-specificity phosphatase
Apoptosis
see apoptosis signaling pathway
GTP-binding protein regulators
see GTP-binding protein regulators
Other
see also deficiencies of intracellular signaling peptides and proteins
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)