The N-terminal and C-terminal domains of a receptor tyrosine phosphatase are associated by non-covalent linkage.

We have cloned the rat homolog of the human leukocyte common antigen-related gene (LAR), which encodes a transmembrane receptor phosphotyrosine phosphatase, and raised antibodies against its protein product. We present evidence here for a processing event resulting in a two-chain structure of the mature receptor on the cell surface. The LAR protein is synthesized as a 190-kDa precursor which is subsequently cleaved into 145-kDa and 85-kDa fragments. The 145-kDa fragment, representing the amino terminus of the protein, is exclusively extracellular and is modified by N-linked glycosylation. The 85-kDa component, derived from the C-terminus of the protein, contains the transmembrane region and intracellular phosphotyrosine phosphatase domains. The two products, associated in a non-covalent manner, comprise the functional LAR cell-surface receptor.