positive regulation of inhibitory G protein-coupled receptor phosphorylation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of inhibitory G protein-coupled receptor phosphorylation. [GO_REF:0000058, GOC:TermGenie, PMID:15937517]

Positive regulation of inhibitory G protein-coupled receptor phosphorylation is a complex biological process that involves a series of molecular events aimed at enhancing the phosphorylation of these receptors. Inhibitory G protein-coupled receptors (GiPCRs) are a class of transmembrane proteins that play a crucial role in signal transduction pathways by coupling to heterotrimeric G proteins, specifically Gi/o proteins, leading to inhibition of adenylyl cyclase activity and downstream signaling cascades.

Phosphorylation of GiPCRs is a key regulatory mechanism that impacts their activity and stability. It can modulate their interactions with G proteins, alter their trafficking within the cell, and influence their degradation. This process is tightly regulated and often involves the interplay of several enzymes and signaling molecules.

Here's a detailed description of the biological process:

1. **Ligand Binding and Receptor Activation:** The process typically begins with the binding of a specific ligand to the GiPCR. This binding event initiates a conformational change in the receptor, exposing intracellular domains and activating its signaling capacity.

2. **Recruitment of Kinases:** Activated GiPCRs can recruit various protein kinases, such as G protein-coupled receptor kinases (GRKs) and other kinases like protein kinase C (PKC), to the cell membrane.

3. **Phosphorylation of the Receptor:** GRKs are a family of kinases specifically designed to phosphorylate activated GPCRs, including GiPCRs, on their intracellular C-terminal tails. These phosphorylation events occur primarily on serine and threonine residues within specific motifs.

4. **Recruitment of Arrestins:** Phosphorylated GiPCRs act as docking sites for arrestin proteins, which bind to the phosphorylated receptor tail. Arrestin binding disrupts the interaction between the GiPCR and its coupled G protein, effectively desensitizing the receptor and preventing further signaling.

5. **Internalization and Degradation:** Arrestin binding also facilitates the internalization of the GiPCR through clathrin-mediated endocytosis. This process involves the sequestration of the receptor-arrestin complex into vesicles and its internalization into the cell. Once inside, the GiPCR can be targeted for degradation in lysosomes or recycled back to the plasma membrane for re-activation.

6. **Regulation of Phosphorylation:** The phosphorylation of GiPCRs is not a one-way street. Phosphatases, such as protein phosphatase 2A (PP2A), can dephosphorylate the receptor, restoring its signaling capacity. This dephosphorylation process allows for the fine-tuning and dynamic regulation of GiPCR signaling.

7. **Other Regulatory Mechanisms:** The phosphorylation of GiPCRs can also be influenced by other factors, including the phosphorylation state of other signaling proteins, cellular localization, and the presence of other interacting molecules.

In summary, positive regulation of inhibitory G protein-coupled receptor phosphorylation involves a complex interplay of ligand binding, kinase recruitment, receptor phosphorylation, arrestin binding, internalization, and dephosphorylation processes. These events ultimately control the signaling activity, trafficking, and stability of GiPCRs, playing a vital role in maintaining cellular homeostasis and responding to diverse stimuli.'
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Proteins (1)

Compounds (3)