ABERRANT SPLICING OF GS-ALPHA TRANSCRIPT IN TRANSFORMED HUMAN ASTROGLIAL AND GLIOBLASTOMA CELL-LINES

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.