INVASIVE HUMAN PITUITARY-TUMORS EXPRESS A POINT-MUTATED ALPHA-PROTEINKINASE-C

Protein kinase-C (PKC) is a ubiquitous eukaryotic kinase that plays a key role in transmembrane signaling and influences important cellular processes, such as proliferation. Increases in its activity and expres sion have been demonstrated in adenomatous human pituitaries with prot ein expression being the highest in invasive tumors (1) Moreover, in t hese same invasive tumors, the mean increase in expression (8.9-fold) does not correlate with the mean increase in activity (2.6-fold), sugg esting a dysfunction in PKC in these tumors. Here, we show that the PK C alpha-isoform (alpha PKC) is overexpressed in human pituitary tumors . The complete sequencing of the PKC cDNA from four invasive tumors ha s revealed a point mutation that is absent in the noninvasive tumors a nalyzed. The point mutation is located at position 294 of the protein, in the V3 region, leading to a substitution of a negatively charged a spartic acid by an apolar glycine. Thus, not only is alpha PKC overexp ressed in human pituitary tumors, but it is also structurally altered in the invasive subpopulation of these tumors.