How is receptor tyrosine kinase activated?

Receptor tyrosine kinases are activated by receptor-specific ligands. Growth factor ligands attach to the EC domains of these kinases, and their receptors are then activated by ligand-induced receptor oligomerization or dimerization. The subsequent release of cis-autoninhibtion also occurs and is required for activation of RTKS. This is because the activation loop and the N-lobe alpha-C helix must take shape in a specific active configuration. When signaling molecules attach to RTKS, they induce adjacent RTKS to inter-link with one another, creating cross-linked dimers. The process of cross-linking activates the tyrosine kinase activity in the RTKs via phosphorylation. Each RTK in the dimer phosphorylates several tyrosines on the alternative RTK. This event is referred to as cross-phosphorylation. RTKs possess the SH2 domain, which attaches to phosphorylated tyrosines in the cytoplasmic RTK receptor tails. Multiple SH2-containing proteins can bind to an activated RTK, allowing concurrent activation of more than one signaling pathway. RTK activation induces alterations in gene transcription, such as point mutations and gene fusions that occur due to chromosomal rearrangements.