There are several mechanisms by which TKRs can become dysregulated: - Gene mutations: Point mutations, deletions, or insertions can lead to constitutive activation of TKRs. - Gene amplification: Overexpression of the TKR gene can result in an increased number of receptors on the cell surface. - Autocrine loops: Cancer cells can produce ligands that activate their own TKRs, promoting continuous signaling. - Fusion proteins: Chromosomal rearrangements can result in fusion proteins that possess constitutive kinase activity.
