Page 2 - 85 cell signalling pathways

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

to form the lipid second messenger PtdIns3,4,5P 3 ation. The ligand Hedgehog (Hh) acts through the
(PIP 3 ). transcription factor GLI.
7. Nitric oxide (NO)/cyclic GMP signalling pathway. 17. Hippo signalling pathway. This pathway has a core
Nitric oxide (NO) synthase (NOS) generates the gas protein kinase cascade that has some similarities to the
NO that acts both through cyclic GMP and nitrosyla- MAP kinase cascade in that a series of serine/threonine
tion reactions. NO has a particularly important role protein kinases function to regulate the transcription
in modulating the activity of other pathways such as of a number of genes that function in cell growth,
Ca 2 + signalling. proliferation and apoptosis.
8. Redox signalling. Many receptors act through 18. Notch signalling pathway. This is a highly conserved
NADPH oxidase (NOX) to form reactive oxygen signalling system that functions in developmental pro-
−• )and cesses related to cell-fate determination particularly in
species, such as the superoxide radical (O 2
hydrogen peroxide (H 2 O 2 ), which act to regulate the stem cells. The notch receptor generates the transcrip-
activity of specific signalling proteins such as tyrosine tion factor NICD (Notch intracellular domain).
phosphatases, transcription factors and ion channels. 19. Endoplasmic reticulum (ER) stress signalling.The en-
−• participates in the nitrosylation reaction in doplasmic reticulum (ER) stress signalling pathway
The O 2
Pathway 7. concerns the mechanisms used by the ER to transmit
9. Mitogen-activated protein kinase (MAPK) signalling. information to the nucleus about the state of protein
This is a classical example of a protein phosphoryla- processing within the lumen of the ER.
tion cascade that often begins with Ras and consists of 20. AMP signalling pathway. This pathway is regulated
a number of parallel pathways that function to control by adenosine monophosphate (AMP), which func-
many cellular processes and particularly those related tions as a metabolic messenger to activate an important
to cell proliferation, cell stress and apoptosis. pathway for the control of cell proliferation.
10. Nuclear factor κB(NF-κB) signalling pathway.This
signalling system has a multitude of functions. It is Not included in Module 2: Figure cell signalling path-
particularly important in initiating inflammatory re- ways are some additional signalling pathways that have
sponses in macrophages and neutrophils as part of an specific functions in regulating various aspects of cell meta-
innate immune response to invading pathogens. bolism, such as sterol sensing and cholesterol biosynthesis,
11. Phospholipase D (PLD) signalling pathway.Thisisa that control the level of cholesterol in cell membranes. An-
lipid-based signalling system that depends upon the other example is found in the NAD signalling pathways,
hydrolysis of phosphatidylcholine by phospholipase where NAD + functions to regulate a number of cellular
D (PLD) to give phosphatidic acid (PA), which func- processes, including energy metabolism, gene transcrip-
tions as a second messenger to control a variety of tion, DNA repair and perhaps ageing as well.
cellular processes. These cassettes then engage a variety of effectors that
12. Sphingomyelin signalling pathway. Certain growth are responsible for activating cellular responses. All of
factors and cytokines hydrolyse sphingomyelin to these mechanisms (Module 1: Figure signal transmission
generate two second messengers that appear to have mechanisms) depend upon information transfer mechan-
opposing effects in the cell. Ceramide seems to pro- isms whereby information is transferred along an orderly
mote apoptosis, whereas sphingosine 1-phosphate sequence of events to activate the internal effectors re-
(S1P) stimulates cell proliferation. S1P may also re- sponsible for inducing a great variety of cellular responses.
lease Ca 2 + from internal stores. The action of S1P is
complicated in that it is released from the cell, where
it can act as a hormone to stimulate external receptors. Cyclic AMP signalling pathway
13. Janus kinase (JAK)/signal transducer and activator of Cyclic AMP is a ubiquitous second messenger that
transcription (STAT) signalling pathway.Thisisafast- regulates a multitude of cellular responses. Cyclic
track signal transduction pathway for transferring in- AMP formation usually depends upon the activation of
formation from cell-surface receptors into the nucleus. G-protein-coupled receptors (GPCRs) that use heterotri-
The Janus kinases (JAKs) are tyrosine kinases that meric G proteins to activate the amplifier adenylyl cyc-
phosphorylate the signal transducers and activators lase (AC), which is a large family of isoforms that dif-
of transcription (STATs), which carry the information fer considerably in both their cellular distribution and
into the nucleus. the way they are activated. There are a number of cyclic
14. Smad signalling pathway. This pathway mediates the AMP signalling effectors such as protein kinase A (PKA),
action of the transforming growth factor β (TGF-β) the exchange proteins activated by cyclic AMP (EPACs)
superfamily, which controls transcription through the that activate the small GTP-binding protein Rap1 and the
Smad transcription factors. cyclic nucleotide-gated channels (CNGCs). These various
15. Wnt signalling pathways. These pathways play an im- effectors are then responsible for carrying out the cyclic
portant role in both development and cell prolifera- AMP signalling functions that include control of metabol-
tion. ism, gene transcription and ion channel activity. In many
16. Hedgehog signalling pathway. This pathway re- cases, these functions are modulatory in that cyclic AMP
sembles the Wnt signalling pathway in that it also often acts to adjust the activity of other signalling path-
functions to regulate development and cell prolifer- ways and thus has a central role to play in the cross-talk

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