Receptor tyrosine kinases and other cell surface proteins (RTK)

Receptor tyrosine kinases (RTKs) and other cell surface proteins represent a vast and heterogeneous group of transmembrane molecules that serve as the primary interface between a cell and its external environment. RTKs are defined by their ability to catalyze the transfer of phosphate groups from ATP to tyrosine residues on target proteins, a process that initiates complex intracellular signaling cascades such as the MAPK and PI3K pathways (Lemmon & Schlessinger, 2010, Cell). This category also encompasses a wide array of other surface proteins, including G protein-coupled receptors and cell adhesion molecules, which collectively regulate nearly every aspect of cellular physiology, including growth, motility, and metabolic homeostasis. In many pathological states, particularly oncology, these proteins are frequently mutated, rearranged, or overexpressed, leading to constitutive signaling that drives disease progression (Du & Lovly, 2018, Cancer Management and Research). Consequently, they are among the most heavily exploited classes of therapeutic targets, with a pharmacological landscape dominated by monoclonal antibodies and small-molecule kinase inhibitors (Yamaoka et al., 2018, International Journal of Molecular Sciences). Despite their clinical success, the therapeutic utility of targeting these proteins is often limited by the emergence of bypass signaling pathways and the necessity of managing systemic toxicities arising from their roles in normal tissue function.

Other names

RTKsCell surface receptorsTransmembrane signaling proteinsSurfaceome

Inhibition of tyrosine kinase activity, competitive inhibition of ATP binding, blockade of ligand-receptor interaction, and induction of receptor internalization or degradation.