Overexpression of protein kinase C beta 1 is not sufficient to induce factor independence in the interleukin-3-dependent myeloid cell line FDC-P1.
To examine whether overexpression of protein kinase C (PKC) is sufficient to allow for factor-independent growth in hematopoietic cells, we used a recombinant retroviral expression vector system to introduce a cDNA encoding the beta 1 isoform of the PKC gene into IL-3-dependent cells FDC-P1. Cell lines were generated which contained up to 24-fold increases in PKC activity. Analysis of these cell lines demonstrated that PKC activation does not play a significant role in IL-3-mediated growth control, as evidenced by the following: (1) IL-3 addition to either overexpressor cell lines did not induce morphologic changes whereas activators of PKC stimulated cellular clumping; (2) early passage FDC-P1 cells, either carrying normal or elevated levels of PKC, were not stimulated to grow by activators of PKC; and (3) addition of phorbol esters or bryostatin 1 to these cells markedly decreased the levels of PKC without affecting the ability of these cells to grow in IL-3. Therefore, we suggest that IL-3 mediated growth occurs through pathways other than involving PKC.
Kraft
A S
AS
Division of Hematology/Oncology, University of Alabama, Birmingham 35294.
Wagner
F
F
Housey
G M
GM
D054713:Bryostatins; D002460:Cell Line; D006133:Growth Substances / Q000494:pharmacology*; D006413:Hematopoietic System / Q000166:cytology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D054713:Bryostatins; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate