Mechanism of mTOR Signaling Pathway
Growth factors are mostly used in this pathway as the first signaling molecule needed for activation. The pathway is activated when these growth factors bind to tyrosine kinase receptors in the cell membrane. Phosphorylation, in which a phosphate group is placed onto the target enzyme to make it active and extend the route to further targets, activates many of the enzymes involved in this pathway.
Following growth factor binding to membrane receptors:
- Phosphorylation activates the PI3 kinase enzyme.
- PIP2 is converted to PIP3 by the enzyme PI3 kinase.
- PIP3 stimulates the Akt enzyme, which in turn stimulates the mTOR protein.
Mechanism of mTOR downstream
- Cellular transformation is linked downstream to the mTOR effectors S6 kinase 1 (S6K1), eukaryotic initiation factor 4E (eIF4E), and eukaryotic initiation factor 4E-binding protein 1 (4EBP1).
- S6K1 phosphorylates several significant targets and is a crucial regulator of cell development.
- S6K1 and eIF4E are both involved in cellular transformation, and studies have connected their overexpression to a bad prognosis for cancer.
Mechanism of mTOR upstream
- Upstream, PI3K/AKT signaling is disrupted by a variety of mechanisms, including growth factor receptor overexpression or activation, such as HER-2 (human epidermal growth factor receptor 2) and IGFR (insulin-like growth factor receptor), PI3K mutations, and AKT mutations/amplifications.
- PTEN, a tumor suppressor and tensin homolog lost on chromosome 10, is a negative regulator of PI3K signaling.
- PTEN expression is reduced in many malignancies and may be downregulated by a variety of processes including mutations, loss of heterozygosity, methylation, and protein instability.
mTOR Signaling Pathway
Cell signaling (cell communication in British English) is the capacity of a cell to receive, process, and transmit messages with its surroundings and with itself. Cell signaling is a basic characteristic of all prokaryotic and eukaryotic cellular life. Cell signaling can take place across short or long distances, and is thus classed as autocrine, juxtacrine, paracrine, and endocrine. Signaling molecules can be produced via a variety of biosynthetic pathways and released by passive or active transporters, as well as cell injury.
Receptors are important in cell signaling because they can sense chemical signals as well as physical inputs. Receptors are proteins that are found on the cell surface or within the cell’s interior, such as the cytoplasm, organelles, and nucleus. Additional enzymatic activity such as proteolytic cleavage, phosphorylation, methylation, and ubiquitinylation may occur as a result of these signaling pathways. Each cell is designed to respond to certain extracellular signal molecules, which serve as the foundation for development, tissue repair, immunology, and homeostasis.