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Identification of the primary growth response gene, ST2/T1, as a gene whose expression is differentially regulated by different protein kinase C isozymes
Author(s) -
Kieser Arnd,
Goodnight JoAnne,
Kölch Walter,
Mischak Harald,
Frederic Mushinski J.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00975-f
Subject(s) - isozyme , protein kinase c , microbiology and biotechnology , gene expression , biology , gene , differential display , transfection , complementary dna , messenger rna , pkc alpha , signal transduction , northern blot , regulation of gene expression , biochemistry , enzyme
Individual protein kinase C isozymes have been shown to play different roles in mediating proliferation, differentiation and transformation, but it is not known to what extent these effects involve induction of expression of particular genes. To explore the differential gene expression that might be induced by activation of different PKC isozymes, we stably transfected NIH 3T3 cells with expression vectors that encode the isozymes PKC‐α, ‐βII, ‐γ, ‐δ, ‐ϵ, ‐ζ and ‐η. Using differential display‐reverse transcription‐polymerase chain reaction we isolated a small cDNA that encodes a portion of the primary response gene, ST2 (also referred to as T1 or DER4), and we confirmed by RNA blot studies that ST2/T1 expression is differentially regulated by PKC isozymes. ST2/T1 mRNA is undetectable in the unstimulated parental NIH 3T3 cells that express only the α isozyme of PKC, but it can be induced by phorbol ester treatment. Clones that overexpress PKC‐α, ‐δ or ‐ϵ similarly do not express ST2/T1 until they are stimulated with phorbol esters, which induces expression of ST2/T1 with kinetics similar to wild‐type NIH 3T3 but to different extents. In contrast, ST2/T1 mRNA is already present in unstimulated cells that overexpress PKC‐βII, ‐γ, ‐ζ and ‐η, but phorbol ester greatly enhances ST2/T1 expression in these cells. These results suggest a differential role for PKC isozymes in mediating the ST2/T1 expression that is induced by growth stimuli.