IDENTIFICATION OF 2 ALTERNATIVELY SPLICED TRANSCRIPTS OF STEP - A SUBFAMILY OF BRAIN-ENRICHED PROTEIN-TYROSINE PHOSPHATASES

A brain-enriched protein tyrosine phosphatase termed STEP(46) (striatal enriched phosphatase) was previously isolated and characterized. Immunological studies with a STEP monoclonal antibody recognized several STEP-immunoreactive proteins, and suggested that additional STEP-related polypeptides existed. This study reports the isolation of two alternatively spliced transcripts of the STEP gene. One of these, STEP(20) (with a predicted molecular mass of 20 M)a) was further characterized and found to lack the conserved tyrosine phosphatase domain. Northern analysis detected a 2.8 kb STEP(20) message in mouse brain. The second alternatively spliced transcript, STEP(61), has a 5'-extended open reading frame that encodes a protein with a predicted molecular mass of 61 kDa and contains a single tyrosine phosphatase domain. The exon-intron organization responsible for the novel STEP(20) and STEP(61) sequences was determined in the mouse STEP genomic DNA. We propose that the original STEP(46), along with STEP(20) and STEP(61), are members of a brain-enriched 61, subfamily of protein tyrosine phosphatases, and that STEP isoforms may have distinct functions within the central nervous system.