MoBio G Protein Effectors Chapter 6

Effectors are the target molecules of G protein α or βγ subunit. Table 6-D-1 lists the major effectors of the α subunit. The βγ subunits may act on adenylyl cyclase, phospholipase A2, phospholipase C, ion channels, calcium ATPase etc.

Adenylyl cyclase

Adenylyl cylase (also known as "adenylate cyclase") catalyzes the conversion of ATP to cAMP, which is an important "second messenger". See The cAMP Signaling Pathway.

Phospholipase A2

Phospholipase A2 (PLA2) cleaves phospholipids, generating arachidonic acid directly (see Figure 6-B-3). Signaling by arachidonic acid is discussed in Section B.

Phospholipase C

Phospholipase C (PLC) also cleaves phospholipids, but at a different site than PLA2, thereby generating diacylglycerol (DAG). There are many types of PLC: β, γ, δ and others. The effector of G protein α and βγ subunits is PLC-β.

Image

Figure 6-D-4. The action of PLC on an unusual phospholipid, PIP2 (phosphatidyl-inositol 4,5-bisphosphate). It generates DAG and IP3 (inositol 1,4,5-trisphosphate). The latter can activate an IP3-sensitive Ca2+ channel in endoplasmic reticulum.

Second messengers

Second messengers are the signaling molecules generated by the stimulation of cell-surface receptors. For example, cAMP, arachidonic acid, DAG and IP3 generated by the activation of G-protein-coupled receptors are second messengers. The agonists which activate G-protein-coupled receptors are first messengers.

Table 6-D-1. Mammalian G protein α subunits.

Class Gene
Variant
Effector Toxin
Sensitivity
Gs αs(s)
αs(L)
(+) Adenylyl cyclase
(+) Ca2+ channel
(-) Na+ channel
Cholera
αolf (+) Adenylyl cyclase Cholera
Gi αi1
αi2
αi3
(-) Adenylyl cyclase
(-) Ca2+ channel
(+) K+ channel
Pertussis
αoa
αob
(-) Ca2+ channel
(+) Phospholipase C
(+) Phospholipase A2
Pertussis
αt1
αt2
(+) cGMP phosphodiesterase Cholera and
Pertussis
αg (+) Phospholipase C Pertussis
α2 (-) Adenylyl cyclase
Gq αq
α11
α14
α15
α16
(+) Phospholipase C
G12 α12
α13
?

Note: "(+)" means "activate" and "(-)" means "inhibit". Upon binding of the cholera toxin, the Gα-bound GTP cannot be converted into GDP so that the G protein remains in the active state. By contrast, pertussis toxin prevents GDP release from the α subunit so that the G protein is locked in the inactive state.