Receptortyrosine

Receptortyrosine, more commonly called receptor tyrosine kinases (RTKs), are a family of transmembrane receptors that possess intrinsic protein tyrosine kinase activity. They detect extracellular signals via ligand-binding domains and transduce signals to the cytoplasm by autophosphorylation of tyrosine residues.

RTKs typically have an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding promotes dimerization or conformational changes, leading to autophosphorylation of specific tyrosines. These phosphotyrosines then serve as docking sites for SH2- or PTB-domain–containing signaling proteins, triggering downstream signaling cascades.

Signaling through RTKs activates several major pathways, including the Ras–MAPK cascade, the PI3K–Akt pathway, PLCγ signaling, and sometimes STAT pathways. Through these routes RTKs influence gene expression, cell growth, differentiation, metabolism, and survival. Adaptor proteins such as Grb2 and Shc help link phosphotyrosines to downstream effectors, coordinating diverse cellular responses. Receptor turnover by endocytosis and lysosomal degradation provides additional regulation, and phosphatases remove phosphates to terminate signaling.

Examples of RTKs include the epidermal growth factor receptor (EGFR/ERBB1), HER2/ERBB2, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), fibroblast growth factor receptors (FGFRs), and the insulin receptor. Proper RTK signaling is essential for development and tissue homeostasis; its dysregulation is linked to diseases such as cancer, diabetes, and metabolic disorders.

Therapeutically, RTKs are targeted by tyrosine kinase inhibitors and monoclonal antibodies, used to treat various cancers and other conditions. Resistance to RTK-targeted therapies can arise through mutations, activation of parallel pathways, or receptor alterations.