Aberrant splicing of Gs alpha transcript in transformed human astroglial and glioblastoma cell lines.

Abstract

Alpha subunits of G proteins, which play a vital role in signal transduction, display considerable structural and functional diversity. Point mutations in two forms of alpha subunits, Gs alpha and Gi2 alpha, impairing their GTPase activity, have been detected in endocrine disorders. We report here the presence of truncated Gs alpha transcripts in a human glioblastoma cell line, HS683, and in an SV40-transformed human astroglial cell line, SVG. These transcripts were detected by polymerase chain reaction (PCR) amplification of cDNAs from the cell lines. The truncated Gs alpha transcripts, with deletions in the central region of the molecule, seem to have originated due to aberrant splicing within exonic sequences, which did not conform to the consensus GT/AG splice signals. The presence of a smaller size protein of mol.wt. around 25,000 kd in the SVG and HS683 cell lines, detected by antibodies specific for the C-terminal region of the Gs alpha subunit, seems to be consistent with the presence of truncated Gs alpha transcripts in these cell lines. These aberrantly spliced transcripts, if translated, could synthesize potentially oncogenic Gs alpha subunits deficient in GTPase activity. Whether such molecules, with sometimes relatively large deletions, retain some aspects of their function and are biologically significant remains to be seen.