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INSRR

The Insulin Receptor-Related Receptor (INSRR) is a protein encoded by the INSRR gene in humans. It is a member of the insulin receptor family, which also includes the insulin receptor (INSR) and the insulin-like growth factor 1 receptor (IGF1R). INSRR is a receptor tyrosine kinase, a type of enzyme that transfers phosphate groups from ATP to specific tyrosine residues on substrate proteins, a key step in signal transduction pathways.

Structure

INSRR is a transmembrane protein that consists of several domains:

• Extracellular domain: This domain is responsible for ligand binding. It is similar in structure to the extracellular domains of INSR and IGF1R, containing leucine-rich repeats and cysteine-rich regions.
• Transmembrane domain: This single-pass domain anchors the receptor in the cell membrane.
• Intracellular domain: This domain contains the tyrosine kinase activity, which is activated upon ligand binding and receptor dimerization.

Function

The precise physiological role of INSRR is not as well understood as that of INSR and IGF1R. However, it is known to be involved in pH sensing and may play a role in cellular responses to changes in extracellular pH. INSRR is expressed in various tissues, including the kidney, where it may contribute to acid-base homeostasis.

Ligands

Unlike INSR and IGF1R, which bind insulin and IGF-1 respectively, the natural ligand for INSRR has not been definitively identified. It is hypothesized that INSRR may respond to changes in extracellular pH rather than binding a specific ligand.

Signaling Pathway

Upon activation, INSRR undergoes autophosphorylation on tyrosine residues, which creates docking sites for downstream signaling molecules. This can lead to the activation of various signaling pathways, including the MAPK/ERK pathway and the PI3K/AKT pathway, which are involved in cell growth, survival, and metabolism.

Clinical Significance

While mutations in INSR and IGF1R are associated with metabolic disorders such as diabetes and growth abnormalities, the clinical implications of INSRR mutations are not well characterized. Research is ongoing to determine the potential role of INSRR in disease and its utility as a therapeutic target.

Research Directions

Current research is focused on elucidating the physiological role of INSRR, identifying its natural ligands, and understanding its involvement in disease processes. Studies are also exploring the potential of targeting INSRR in therapeutic interventions.

Also see

• Insulin receptor
• Insulin-like growth factor 1 receptor
• Receptor tyrosine kinase
• Signal transduction

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