Activation of transcription via AP-1 or CREB regulatory sites is blocked by protein tyrosine phosphatases.
Transcriptional activation endowed by AP-1 or CREB binding sites can be significantly reduced in transient transfection tests by expression from the corresponding cloned cDNAs of protein tyrosine phosphatases. Both the protein tyrosine phosphatase 1B and the T-cell protein tyrosine phosphatase, as well as a novel form of this latter protein generated by an alternative splicing even show this activity. The effect is specific, as none of the protein tyrosine phosphatases alters transcriptional activation by either the estrogen receptor, GAL4, or a GAL4-VP16 fusion protein. Furthermore, the activities of the SV40 early gene promoter and a Moloney murine leukemia virus long terminal repeat promoter are not reduced by these phosphatases. We conclude that a yet to be identified protein phosphorylated on tyrosine is necessary for a full transcriptional response via AP-1 or CREB binding sites.
Champion-Arnaud
P
P
Faculté des Sciences et des Techniques, Université de Nantes, France.
Gesnel
M C
MC
Foulkes
N
N
Ronsin
C
C
Sassone-Corsi
P
P
Breathnach
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D016391:Genes, src; D006801:Humans; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D004247:DNA; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3