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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 9

Module 2: Table heterotrimeric G proteins
The heterotrimeric proteins are assembled from subunits taken from the G protein α (Gα), G protein β (Gβ) and G protein γ (Gγ) families.
Heterotrimeric G protein Function
Gprotein α (Gα) subunits
Gα s Stimulate adenylyl cyclase
Gα olf Stimulate adenylyl cyclase
Gα i1 Inhibit adenylyl cyclase
Gα i2 Inhibit adenylyl cyclase
Gα i3 Inhibit adenylyl cyclase
Gα o1 Inhibit adenylyl cyclase
Gα o2 Inhibit adenylyl cyclase
Stimulate cyclic GMP phosphodiesterase in rod photoreceptors
Gα t1
Stimulate cyclic GMP phosphodiesterase in rod photoreceptors
Gα t2
Gz Close K + channels. Inhibits exocytosis (see Module 10: Figure lactotroph regulation)
Stimulate phospholipase Cβ (PLCβ)(see Module 10: Figure taste receptor cells and Module 7:
Gα gust
Figure L cells)
Stimulate phospholipase Cβ (PLCβ)
Gα q
Stimulate phospholipase Cβ (PLCβ)
Gα 11
Stimulate phospholipase Cβ (PLCβ)
Gα 14
Stimulate phospholipase Cβ (PLCβ)
Gα 15
Gα 16 Stimulate phospholipase Cβ (PLCβ)
Gα 12 Stimulate RhoGEFs to activate Rho (Module 2: Figure Rho signalling)
Gα 13 Stimulate RhoGEFs to activate Rho (Module 2: Figure Rho signalling)
Gprotein β (Gβ) subunits; β1--β5 These β subunits combine with γ subunits to form βγ dimers that have a number of control functions
(for details see Module 2: Figure heterotrimeric G protein signalling)
Gprotein γ (Gγ) subunits; γ1--γ11 These γ subunits combine with β subunits to form βγ dimers that have a number of control functions
(for details see Module 2: Figure heterotrimeric G protein signalling)
arrestin that prevent the heterotrimeric proteins from (PTB), pleckstrin homology (PH) and phox homology
binding the receptor and this leads to receptor desensit- (PX) domains, indicating that, in addition to their GAP
ization (Module 1: Figure homologous desensitization). activity, they may have other functions. One of these might
The active Gα/GTP and Gβγ subunits are able to re- be the regulation of the G-protein-activated inwardly rec-
lay information to a large number of signalling pathways, tifying K + (GIRK) channel.
which are described in more detail for the different sig- The function of RGS proteins has been clearly defined
nalling pathways: in phototransduction, where RGS9 acts to accelerate GTP
hydrolysis by Gα t (step 6 in Module 10: Figure photo-
• The cyclic AMP signalling pathway (Module 2: Figure transduction).
cyclic AMP signalling).
• The activation of phospholipase Cβ (PLCβ)inthe
Monomeric G proteins
inositol 1,4,5-trisphosphate (InsP 3 )/Ca 2 + signalling
The monomeric GTP-binding proteins (G proteins) be-
cassette (Module 2: Figure PLC structure and function).
long to a large family of approximately 150 members. Ras
• Modulation of the Ca V 2 family of N-type and P/Q-type
was the founding member, and the family is often referred
channels (Module 3: Figure Ca V 2 channel family).
to as the Ras family of small G proteins. Within this family,
• Activation of the PtdIns 3-kinase signalling pathway
it is possible to recognize five subfamilies: Ras, Rho, Rab,
(Module 2: Figure PtdIns 3-kinase signalling). Ran and ADP-ribosylation factor (Arf) (Module 2: Table
• Activation of phosphodiesterase 6 (PDE6) during pho- monomeric G protein toolkit). The Ran family plays a role
totransduction in photoreceptors (Module 10: Figure in nuclear transport, whereas the large Rab family func-
phototransduction). tions in membrane trafficking. The Ras and Rho family are
• Gα olf functions in sperm motility and chemotaxis. primarily involved in cell signalling, where they function as
• Gα gust , which is also known as gustudin, functions in binary switches to control a number of cell signalling sys-
taste cells and in the L cells that detect food components tems. This binary switch is driven by the binding of GTP,
in the lumen of the intestine L cells (Module 7: Figure which represents the ON reaction, and is followed by the
L cells).
hydrolysis of the GTP by the endogenous GTPase activ-
Regulators of G protein signalling (RGS) ity. Most attention has focused on a small number of these
The regulators of G protein signalling (RGS) are a large signal transducers, and the following will be described in
family of approximately 30 proteins that function as detail to illustrate their role in cell signalling:
GTPase-activating proteins (GAPs) for the heterotrimeric
Gproteins(Module 2: Figure heterotrimeric G protein sig- • Arf signalling mechanisms
nalling). The Gα subunit has a low intrinsic GTPase activ- • Cdc42 signalling mechanisms
ity and this is greatly increased by the RGS proteins. RGS • Rab signalling mechanisms
structure is defined by an RGS-box region that is respons- • Rac signalling mechanisms
ible for binding to Gα/GTP. However, many of the RGS • Ras signalling mechanisms
proteins contain a number of other protein--protein inter- • Rap signalling mechanisms
action domains, such as PDZ, phosphotyrosine-binding • Rho signalling mechanisms

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