GROWTH FACTOR-INDUCIBLE ALTERNATIVE SPLICING OF NONTRANSMEMBRANE PHOSPHOTYROSINE PHOSPHATASE PTP-1B PREMESSENGER RNA

PTP-1B is a major nontransmembrane phosphotyrosine phosphatase in huma n cell lines and tissues, but its physiological function(s) and mechan ism(s) of regulation are largely unknown. We have found that in human diploid fibroblasts a novel PTP-1B mRNA isoform is produced upon stimu lation of quiescent cells with a variety of growth factors. Generation of this isoform requires protein synthesis, suggesting that the produ ct(s) of an immediate early response gene(s) is required. RNase protec tion and reverse transcription polymerase chain reaction analysis demo nstrate that the isoform arises as a consequence of alternative pre-mR NA splicing, leading to retention of the last intron. The novel isofor m is found on polyribosomes, indicating that it is actively translated , and is variably expressed in human tissues. Sequence analysis indica tes that the isoform encodes a PTP-1B protein with an altered C termin us. To our knowledge, this is the first example of growth factor-regul ated alternative splicing.