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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 1

Module 2

Cell Signalling Pathways

Synopsis

Cells use a large number of clearly defined signalling pathways to regulate their activity. In this module,
attention is focused on the On mechanisms responsible for transmitting information into the cell. These
signalling pathways fall into two main groups depending on how they are activated. Most of them are
activated by external stimuli and function to transfer information from the cell surface to internal effector
systems. However, some of the signalling systems respond to information generated from within the
cell, usually in the form of metabolic messengers. For all of these signalling pathways, information is
conveyed either through protein--protein interactions or it is transmitted by diffusible elements usually
referred to as second messengers. Cells often employ a number of these signalling pathways, and
cross-talk between them is an important feature. In this section, attention is focused on the properties
of the major intracellular signalling pathways operating in cells to regulate their cellular activity.
During the processes of development, specific cell types select out those signalling systems that are
suitable to control their particular functions. One of the aims of this website is to understand how these
unique cell-specific signalsomes function to regulate different mammalian cell types.

Intracellular signalling pathways 1. Cyclic AMP signalling pathway. One of the first sig-
There are a large number of intracellular signalling path- nalling systems to be characterized was the cyclic
ways responsible for transmitting information within the AMP signalling pathway, which led to the second mes-
cell. They fall into two main categories. The majority re- senger concept that applies to many other signalling
spond to external stimuli arriving at the cell surface, usu- systems. The idea is that the external stimulus arriving
ally in the form of a chemical signal (neurotransmitter, at the cell surface is the first messenger, which is then
hormone or growth factor), which is received by recept- transformed at the cell surface by adenylyl cyclase
ors at the cell periphery that function as molecular an- (AC) into a second messenger, cyclic AMP, which is
tennae embedded in the plasma membrane. These recept- part of the signalling cascade that then activates down-
ors then transfer information across the membrane using stream effectors.
a variety of transducers and amplifiers that engage a di- 2. Cyclic ADP-ribose (cADPR) signalling and nicotinic
verse repertoire of intracellular signalling pathways (Path- acid–adenine dinucleotide phosphate (NAADP) sig-
ways 1--16 in Module 2: Figure cell signalling pathways). nalling systems function in Ca 2 + signalling. An ADP--
The phosphoinositide signalling and Ca 2 + signalling sys- ribosyl cyclase (ADP-RC) is responsible for generat-
tems (Pathways 2--6) have been grouped together because ing these two second messengers.
they contain a number of related signalling pathways that 3. Voltage-operated channels (VOCs) contribute to
often interact with each other. The other categories are Ca 2 + signals by controlling the entry of external Ca 2 +
the pathways that are activated by signals generated from in excitable cells.
within the cell (Pathways 17 and 18). There are a number of 4. Receptor-operated channels (ROCs) contribute to
metabolic messengers that act from within the cell to initi- Ca 2 + signals by controlling Ca 2 + entry in both excit-
ate a variety of signalling pathways. GTP-binding proteins able and non-excitable cells.
often play a central role in the transduction process re- 5. Stimuli that activate phospholipase C (PLC) to hy-
sponsible for initiating many of these signalling pathways. drolyse PtdIns4,5P 2 (also known as PIP 2 ) generate a
All of these signalling pathways generate an internal number of signalling pathways:
messenger that is responsible for relaying information to • Inositol 1,4,5-trisphosphate (InsP 3 )/Ca 2 + sig-
the sensors that then engage the effectors that activate cel- nalling cassette
lular responses. The main features of the signalling path- • Diacylglycerol (DAG)/protein kinase C (PKC) sig-
ways summarized in Module 2: Figure cell signalling path- nalling cassette
ways are outlined below: • PtdIns4,5P 2 signalling cassette
• Multipurpose inositol polyphosphate signalling
Green text indicates links to content within this module; blue text pathway
indicates links to content in other modules.
6. PtdIns 3-kinase signalling is activated by stimuli
Please cite as Berridge, M.J. (2012) Cell Signalling Biology;
doi:10.1042/csb0001002 that stimulate PtdIns 3-kinase to phosphorylate PIP 2

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