Page 3 - 85 cell signalling pathways

Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 3

Module 2: Figure cell signalling pathways

1 AC cAMP
2 ADP-RC NAADP
cADPR
3 VOC Ca 2+

4 ROC
IP
3 DAG
5 PLC
PIP 2
S
R 6 PI 3-K PIP 3
E S
C cGMP E
U 7 NOS NO S
D Nitrosylation N
S O
N 8 NOX O 2 + H O 2 P
2
A S S
I S R E
L R JNK
U T R TO R
M & 9 Ras Erk1/2 O R
I S C A
T S p38 N E L
S R 10 IkBs NF-kB E F U
TO S F E L L
P 11 PLD PA E
E 12 C
C Smase ceramide/ S1P
E
R 13 JAK STAT
14 TGF- Smad
15 Wnt b-catenin
16 Hh GLI
17 MST1/2 Lats1/2 YAP
18 Notch NICD
ATF6, PERK
ER 19
SCAP, bHLH
Metabolism 20 AMP AMPK

Summary of the major signalling pathways used by cells to regulate cellular processes.
Cells have a number of signalling systems that are capable of responding either to external stimuli or to internal stimuli. In the case of the former, external
stimuli acting on cell-surface receptors are coupled to transducers to relay information into the cell using a number of different signalling pathways
(Pathways 1--17). Internal stimuli derived from the endoplasmic reticulum (ER) or from metabolism activate signalling pathways independently of
external signals (Pathways 18 and 19). All of these pathways generate an internal messenger that then acts through an internal sensor to stimulate
the effectors that bring about different cellular responses. As described in the text, the names of these signalling pathways usually reflect a major
component(s) of the pathway.

between signalling pathways. This modulatory function is zyme adenylyl cyclase (AC) (Module 2: Figure heterotri-
particularly evident in the case of Ca 2 + signalling in both meric G protein signalling). In the case of AC stimulation,
neuronal and muscle cells. Many of the functions of cyclic the external stimulus binds to the GPCR that functions
AMP depend upon the precise location of PKA relative as a guanine nucleotide exchange factor (GEF) to replace
to both its upstream and downstream effectors. A family GDP with GTP, which dissociates the heterotrimeric com-
of A-kinase-anchoring proteins (AKAPs) determines this plex into their Gβγ and Gα subunits (Module 2: Figure
cellular localization of PKA as well as a number of other cyclic AMP signalling). The Gα S ·GTP complex activates
signalling components. The OFF reactions responsible for AC, whereas Gα i ·GTP inhibits AC. The Gα subunits have
removing cyclic AMP are carried out by either cyclic AMP GTPase activity that hydrolyses GTP to GDP, thus ter-
hydrolysis or by cyclic AMP efflux from the cell. minating their effects on AC. The endogenous GTPase of
Gα S ·GTP is inhibited by cholera toxin and this causes the
persistent activation of the intestinal fluid secretion that
Cyclic AMP formation
results in the symptoms of cholera.
The formation of cyclic AMP can be activated by a
very large number of cell stimuli, mainly neurotrans-
mitters and hormones (Module 1: Figure stimuli for Adenylyl cyclase (AC)
cyclic AMP signalling). All these stimuli are detec- The adenylyl cyclase (AC) family is composed of ten iso-
ted by G-protein-coupled receptors (GPCRs) that use forms: nine of them are membrane-bound (AC1--AC9),
heterotrimeric G proteins, which are the transducers that while one of them is soluble (AC10) (Module 2: Table
are responsible for either activating or inhibiting the en- adenylyl cyclases). The domain structure of AC1--AC9 is

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