regulation of insulin-like growth factor receptor signaling pathway

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of insulin-like growth factor receptor signaling. [GOC:bf]

The insulin-like growth factor receptor (IGFR) signaling pathway plays a crucial role in regulating cell growth, proliferation, differentiation, and survival. Its dysregulation is implicated in various diseases, including cancer and metabolic disorders. The pathway is initiated upon binding of insulin-like growth factors (IGFs), including IGF-1 and IGF-2, to their respective receptors, IGFR1 and IGFR2. This binding triggers receptor dimerization and autophosphorylation, creating docking sites for downstream signaling molecules. Key components of the IGFR pathway include:

- **Insulin Receptor Substrate (IRS) proteins:** IRS proteins are adaptor molecules that bind to phosphorylated IGFRs and serve as docking platforms for other signaling proteins.
- **Phosphatidylinositol 3-kinase (PI3K):** PI3K is recruited to IRS proteins and phosphorylates phosphatidylinositol (PIP2) to produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3).
- **Protein kinase B (Akt):** Akt is a serine/threonine kinase activated by PIP3 through the phosphoinositide-dependent kinase 1 (PDK1). Akt plays a central role in the pathway, promoting cell survival, growth, and metabolism.
- **Mammalian target of rapamycin (mTOR):** mTOR is a downstream target of Akt and regulates protein synthesis, cell growth, and autophagy.
- **Ras/mitogen-activated protein kinase (MAPK) pathway:** The IGFR can also activate the Ras/MAPK pathway, contributing to cell proliferation and differentiation.

The regulation of the IGFR signaling pathway is tightly controlled by various mechanisms:

- **Ligand availability:** IGF-1 and IGF-2 levels are regulated by growth hormone, nutritional status, and other factors.
- **Receptor expression:** IGFR1 and IGFR2 expression is influenced by developmental stage, tissue type, and external stimuli.
- **Negative feedback loops:** The pathway is subject to negative feedback mechanisms that prevent excessive signaling. For example, Akt can phosphorylate IRS proteins, reducing their ability to activate downstream signaling.
- **Protein phosphatases:** Phosphatases dephosphorylate IGFRs and downstream signaling components, terminating pathway activation.
- **Ubiquitination and proteasomal degradation:** IGFRs and other signaling components are targeted for degradation by the ubiquitin-proteasome system.

The IGFR signaling pathway is highly complex and interconnected with other signaling pathways, allowing for precise control of cell behavior. Dysregulation of this pathway can lead to various diseases, highlighting its critical role in human health.'
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Proteins (6)

Compounds (3)