Cell signaling and cAMP-mediated pathway

Cell signaling and its types

Cell signaling is referred to as the communication between various cells and molecules. The two most important part of cell signaling is a ligand and a receptor. A ligand is a molecule that is a primary messenger that binds to a specific receptor on the cell and transduces a signaling cascade inside the cell which infers a specific function in the downstream.

The mode of signaling can be of broadly three types:

  1. Autocrine signaling: In this type, the ligand that is secreted by a cell has the binding receptor on that same particular cell.
  2. Paracrine signaling: The cell having the receptor for the ligand is in close proximity to the cell secreting the ligand.
  3. Endocrine signaling: The ligand needs to travel through the bloodstream in order to find the cell that is having its particular receptor. This is seen in the case of hormones.

Types of receptors: There are three types of receptors that are found on the cell surface.

  1. Enzyme receptors: These have a catalytic domain inside the receptor which catalyzes a reaction that initiates the signaling of the downstream.
  2. G-protein coupled receptors: These are a specific group of receptors that function by activating a specific protein called the G protein.
  3. Ion channel gated receptors: These are activated to move certain ions in and out of the cell to maintain the potential difference of the membrane.

Cell signaling and cAMP-mediated pathway


G-protein coupled receptor and the cAMP-mediated pathway

The G-protein coupled receptor or GPCR is a 7-alpha helical transmembrane receptor with an extracellular ligand-binding domain, 7 transmembrane domains, and an intracellular G-protein binding domain. The whole receptor spans the cell membrane seven times and hence the name.

When a ligand binds to the extracellular ligand-binding domain, there is a series of conformational changes in the whole receptor and it is ready to activate the G-protein.

The trimeric G-protein

The G-protein in the case of the cAMP-mediated pathway is a trimeric protein. It is also called the Gs protein. The “s” stands for “stimulatory”. The trimeric G protein has an alpha, a beta, and a gamma subunit. The G protein is named so because it has an inherent GTPase activity whereby it can hydrolyze GTP into GDP and Pi. Normally in its inactive form, the alpha subunit is bound to GDP. When it comes in contact with the active GPCR, the confirmation of the G-protein alters and the GDP is replaced by GTP. Now the protein is in an active state. This causes the alpha subunit to dissociate from the beta and gamma subunits.

Transduction by secondary messenger

The alpha subunit goes on to activate a membrane-bound protein called adenylyl cyclase. This enzyme produces cAMP from ATP molecules. The cAMP molecules are referred to as secondary messengers. The cAMP activates a protein called PKA (Protein Kinase A). PKA has two catalytic subunits which are initially bound to two regulatory subunits and the protein is inactivated. Binding of cAMP causes the regulatory subunits to fall off and PKA is activated. PKA can move inside the nucleus and can cause the activation of a nuclear protein called CREB (cAMP Receptor Element Binding protein). The CREB protein is a transcriptional regulator can bind to specific regions of the DNA called CRE regions causing the transcription of specific genes that confer specific functions.


  1. Cell and Molecular Biology – Concepts and Experiments (7th Ed)
  2. Molecular Biology of the Cell – 6 edition

Cell signaling and cAMP-mediated pathway

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