NOVEL ALTERNATIVE SPLICING PREDICTS A SECRETED EXTRACELLULAR ISOFORM OF THE HUMAN RECEPTOR-LIKE PROTEIN-TYROSINE-PHOSPHATASE LAR

RT-PCR was used to examine the expression of LAR (encoding the leucocy te-common antigen-related protein tyrosine phosphatase) in normal huma n colon mucosa, and colon polyps and tumors. Although the LAR protein was not detected in the colon in a previous immunohistochemical study, amplification of a region of LAR between the most membrane proximal ( eighth) fibronectin type-III (FN-III) repeat and the transmembrane dom ain demonstrated LAR expression in all samples, but showed no differen ce in expression within matched samples from each patient examined. An additional minor fragment amplified in all reactions was consistently observed in colon and various cell line samples using this and two ot her LAR-specific sets of primers. Cloning and sequencing of the fragme nt identified it as deriving from a novel alternatively spliced form o f LAR containing a retained intron of 85 bp. This intron encodes an ad ditional 13 amino acids followed by an in-frame stop codon, thus its r etention is predicted to give rise to a secreted LAR extracellular reg ion isoform(s). LAR transcripts containing the intron were detected by RNase protection assay of colon samples and were present in most huma n tissues examined by Northern analysis. A protein in colon tumor extr act was recognized by antiserum raised to the intron-encoded sequence. Soluble isoforms of the LAR extracellular immunoglobulin (Ig)-like/FN -III repeat-containing region could have a biological function distinc t from those isoforms localized at the cell surface and/or coupled to intracellular phosphatase activity.