A novel isoform of the low molecular weight phosphotyrosine phosphatase, LMPTP-C, arising from alternative mRNA splicing.
The low molecular weight protein tyrosine phosphatase (LMPTP) is an 18-kDa enzyme that it distantly related to other protein tyrosine phosphatases. The single gene for LMPTP is known to undergo an alternative splicing event in which exon 3 or exon 4 is excised, resulting in two isoforms termed A and B; the latter is more mobile in SDS/PAGE. In this paper we report the existence of a third isoform, which we call C, in which both exons 3 and 4 are lacking. We find the resulting mRNA to be ubiquitously expressed at levels that exceed those of the mRNAs for isoforms A and B. This mRNA was reverse-transcribed, cloned and sequenced, confirming the direct splicing of exon 2 to exon 5. In-vitro transcription and translation of the cDNA for the novel isoform resulted in the expected 16 kDa protein. This protein was also detected in Jurkat T cells using an antipeptide antiserum. LMPTP-C immunoprecipitated from transfected cells, as well as bacterially produced recombinant LMPTP-C, lacked phosphatase activity. Unlike LMPTP-B, LMPTP-C was not phosphorylated on tyrosine when coexpressed with Lck despite the presence of the two acceptor tyrosines. Finally, whereas c-fos induction by platelet-derived growth factor was inhibited by LMPTP-B, LMPTP-C augmented it. These results suggest that the lack of the 38-amino acid fragment encoded by exon 3 or 4 results in a protein product with a different three-dimensional folding, that lacks a functional catalytic pocket and that may function as a natural antagonist of isoforms A and B.
Tailor
P
P
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA. tmustelin@skcc.org
Gilman
J
J
Williams
S
S
Mustelin
T
T
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008970:Molecular Weight; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
D017931:DNA Primers; D007527:Isoenzymes; D012333:RNA, Messenger; D017027:Protein Tyrosine Phosphatases