What are the key components of cell signaling?2017-11-02T10:20:29+08:30

What are the key components of cell signaling?



There are many components that facilitate cell signaling. Although the full array of individual molecules cannot be discussed in detail here, the functions or roles that they play can be described. In some cases the protein components may serve as receptors, in other cases they may act as intracellular messengers, or, they may serve as sensors or effectors.


Receptors are proteins that interact with specific ligands and transmit the resulting signals to the cell interior. These proteins are most often transmembrane, with an extracellular domain for ligand binding and an intracellular domain that is often chemically linked to a downstream signaling pathway. Binding of a ligand to the extracellular region of a receptor often initiates a conformational change within the cytosolic domain and this initiates a series of biochemical reactions known as signal cascades. These signal cascades pass the signal from one molecule to another before a cellular response is achieved

Receptors can be broadly classified into three categories.

  1. G-protein coupled receptor (GPCRs).
  2. Ion channels
  3. Enzyme-linked receptors

As the name suggests, GPCRs are linked to a monomeric or trimeric G-protein via their cytosolic domain. Activation of GPCRs, which results from GDP to GTP exchange within this linked G-protein, subsequently activates a range of kinases which in turn facilitate phosphorylation events on target proteins.

Similarly, activation of an ion channel also occurs through interactions with a ligand and also induces a conformational change within the protein. In this case however, the protein will acquire an open conformation that permits the ions to flow into the cell. Ion channels usually transport a specific type of ion, with Na+, K+, Ca2+ and Cl- being the most common that are associated with ‘information flow’ or signal transduction. Being associated with electrical signaling, ion channels are most commonly observed in muscle and brain cells.

It should be noted that intracellular receptors, such as steroid receptors, are also relevant to signal transduction. These receptors are activated by hydrophobic ligands that can pass through the lipid membrane and therefore enter the cell passively. Nitric oxide gas and steroids like estrogen are examples of such ligands.

Intracellular messengers

Intracellular messengers, or secondary messengers, are the intermediate proteins or small molecules that carry a signal from the receptor to intracellular sensors and effectors. For every one receptor that is activated, multiple intracellular messenger molecules are activated and therefore it is at this stage that the signal is said to be amplified. Examples of intracellular messengers include calcium ions, enzymes such as adenylyl cyclase, or lipids such as inositol triphosphate, etc [1][2][3] . One key superfamily of intracellular messengers are the Small GTPases. It should be noted that it is rare for these molecules to function alone. Instead, each intracellular messenger will act within a larger signaling pathway.

Sensors and effectors

Considered the final stage in the signaling pathway or cascade, the sensor and effector proteins are responsible for the cell’s response to the signal. These may promote processes such as exocytosis, endocytosis, migration, actin remodeling, gene expression, etc.

Examples include transcription factors which induce gene expression or actin binding proteins which induce actin remodeling, cell migration, etc.

Off mechanisms

Cells do not respond to any one signal continuously. Instead many signal pathways are controlled by ‘molecular switches’ that can switch off a given response should they become detrimental to the required cell state or function. This may be achieved via a number of mechanisms.

For example, receptors may be desensitized to the ligand, as is commonly seen for ion channels. The intracellular signaling molecules can also be degraded. This occurs, for example, with lipids such as IP3 which are metabolized by inositol phosphatases, and cyclic AMP / cyclic GMP which are degraded by phosphodiesterases. In another mechanism, Ca2+ ions are pumped back into calcium stores by pumps, thus restoring their normal concentrations in the cytosol. These mechanisms ensure that the cellular response is controlled by inhibiting the flow of information, and stalling the cellular response even after cellular detection of a given signal.

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  1. Bhatnagar S, and Kumar A. Therapeutic targeting of signaling pathways in muscular dystrophy. J. Mol. Med. 2009; 88(2):155-66. [PMID: 19816663]
  2. Rando TA. The dystrophin-glycoprotein complex, cellular signaling, and the regulation of cell survival in the muscular dystrophies. Muscle Nerve 2001; 24(12):1575-94. [PMID: 11745966]
  3. Morganti A, Sala C, Turolo L, Palermo A, and Zanchetti A. Participation of the renin-angiotensin system in the maintenance of blood pressure during changes in posture in patients with essential hypertension. J. Hypertens. 1985; 3(1):55-61. [PMID: 2987342]