PTPRs

Protein tyrosine phosphatase receptors (PTPRs) are a family of receptor-type protein tyrosine phosphatases characterized by an extracellular ligand-binding region, a single transmembrane helix, and one or two intracellular phosphatase domains. They regulate signaling by removing phosphate groups from tyrosine residues on substrate proteins and participate in diverse processes such as development, neural differentiation, and cell–cell adhesion. In humans, multiple PTPR genes exist, including PTPRD, PTPRS, PTPRG, PTPRJ, and PTPRZ1.

Structure: The extracellular region of many PTPRs contains immunoglobulin-like and fibronectin type III repeats; the exact composition varies among family members. The single transmembrane domain anchors the receptor in the plasma membrane. The intracellular region typically contains two phosphatase domains (D1 and D2); D1 is the primary catalytic domain, whereas D2 is often less active or regulatory. Alternative splicing yields multiple isoforms with distinct signaling properties.

Function: PTPRs participate in receptor-mediated signaling by dephosphorylating tyrosine residues on various substrates, thereby modulating pathways that control cell adhesion, migration, proliferation, and differentiation. Through their extracellular regions, they can influence cell–cell contact and interactions with extracellular matrix components, linking external cues to intracellular signaling networks, particularly in the nervous system and during development.

Clinical relevance: Aberrant expression or mutation of PTPR genes has been reported in several cancers and neurodevelopmental disorders, underscoring their roles as tumor suppressors or modulators of signaling. For example, some PTPR family members are studied for contributions to glioma biology, colorectal cancer, and psychiatric or cognitive disorders, though the effects are context dependent and under active investigation.