Receptor Tyrosine Kinases (RTKs) and Receptor Protein Tyrosine Phosphatases (RPTPs) in Mammalian Signal Transduction: When Opposites Attract

Protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) constitute two major superfamilies of signaling enzymes in mammals, displaying comparable genomic representation (~100 genes each) and numbers of catalytically active proteins (~80 enzymes each). Both families include receptor and non-receptor forms; however, their distributions differ substantially. PTKs comprise approximately 58 receptor tyrosine kinases (RTKs), whereas PTPs include only circa 21 receptor protein tyrosine phosphatases (RPTPs). Despite these differences, RTKs and RPTPs share a common structural organization consisting of (i) an extracellular domain responsible for ligand recognition; (ii) a single-pass transmembrane domain anchoring the receptor to the plasma membrane; and (iii) an intracellular catalytic domain containing either kinase or phosphatase activity. Signal transduction mediated by RTKs and RPTPs generally depends on ligand binding and receptor dimerization. Remarkably, although these receptor families regulate signaling through fundamentally opposite molecular mechanisms, both are essential for controlling cell proliferation, adhesion, migration, differentiation, development, and survival. RTKs have been more extensively characterized than RPTPs; nevertheless, both receptor classes function as critical regulators of intercellular and intracellular communication pathways. Moreover, their membrane-associated localization makes them attractive targets for therapy in multiple human diseases, particularly cancer and neurological disorders.