receptor guanylyl cyclase signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:mah, GOC:signaling, PMID:16815030]

The receptor guanylyl cyclase (GC) signaling pathway is a crucial intracellular signaling cascade involved in various physiological processes, particularly in the cardiovascular, renal, and digestive systems. This pathway is initiated by the binding of a specific ligand to a receptor guanylyl cyclase, leading to a cascade of events that ultimately regulate cellular function. Here's a detailed breakdown:

1. Ligand Binding and Receptor Activation: The pathway begins with the binding of a specific ligand to its cognate receptor guanylyl cyclase. These ligands can include:

- **Natriuretic peptides (NPs):** These peptides, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are primarily involved in regulating blood pressure, fluid balance, and cardiovascular function. They bind to natriuretic peptide receptors (NPRs), which are receptor guanylyl cyclases.

- **Guanylin and Uroguanylin:** These peptides, produced in the gastrointestinal tract, play a role in regulating intestinal fluid and electrolyte balance. They bind to guanylin receptors (GC-C), also known as guanylate cyclase C.

2. Receptor Dimerization and Activation: Upon ligand binding, receptor guanylyl cyclases undergo a conformational change, typically involving dimerization. This dimerization activates the enzymatic activity of the receptor.

3. Cyclic GMP Production: Activated receptor guanylyl cyclases catalyze the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). cGMP acts as a second messenger, triggering downstream signaling events.

4. cGMP-Dependent Protein Kinase (PKG) Activation: cGMP binds to and activates cGMP-dependent protein kinase (PKG). PKG is a serine/threonine kinase that phosphorylates various downstream targets, mediating diverse cellular responses.

5. Downstream Signaling and Cellular Effects: The activation of PKG leads to a wide range of cellular effects, including:

- **Vasodilation:** PKG phosphorylates and inactivates myosin light chain kinase (MLCK), reducing smooth muscle contraction and promoting vasodilation.

- **Natriuresis and Diuresis:** PKG promotes natriuresis (sodium excretion) and diuresis (increased urine production) by affecting renal tubular function and blood pressure regulation.

- **Inhibition of Cell Growth and Proliferation:** PKG can suppress cell growth and proliferation by influencing gene expression and cell cycle regulation.

- **Regulation of Intestinal Fluid and Electrolyte Balance:** PKG plays a role in regulating intestinal fluid and electrolyte balance, contributing to diarrhea and other gastrointestinal functions.

6. cGMP Degradation: The signaling pathway is terminated by the degradation of cGMP by phosphodiesterases (PDEs). PDEs hydrolyze cGMP to GMP, reducing its intracellular concentration and ending the signaling cascade.

7. Receptor Internalization and Desensitization: After ligand binding and activation, receptor guanylyl cyclases can be internalized and degraded, reducing the responsiveness of the cell to further stimuli. This process helps to regulate the duration and intensity of the signaling pathway.

In summary, the receptor guanylyl cyclase signaling pathway is a complex and versatile signaling cascade that plays crucial roles in various physiological processes. The pathway is activated by specific ligands, leading to cGMP production and subsequent activation of PKG, which orchestrates diverse cellular responses. The pathway is tightly regulated by mechanisms that control cGMP levels, receptor internalization, and downstream signaling events. Dysregulation of this pathway has been implicated in various diseases, including cardiovascular diseases, renal diseases, and gastrointestinal disorders.'
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Proteins (2)

Compounds (4)