Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP.
We have purified and characterized the 50 kd activator protein 2 (AP-2), another enhancer-binding protein interacting with the human metallothionein IIA (hMT-IIA) gene control region. Purified AP-2 activates transcription in vitro from a hybrid promoter containing hMT-IIA upstream sequences. AP-2 also recognizes control elements of the human growth hormone, c-myc, and H-2Kb genes, and the SV40 and bovine papilloma virus enhancers. Multiple synthetic copies of the hMT-IIA high-affinity AP-2 binding site can act as efficient, cell-type-specific enhancer elements; their activity increases after treatment of cells with phorbol ester or cAMP-elevating agents. In contrast, a synthetic enhancer recognized by factor AP-1 is activated only by phorbol ester. AP-2 appears to mediate transcriptional activation in response to two different signal-transduction pathways, one involving the phorbol-ester- and diacylglycerol-activated protein kinase C, the other involving cAMP-dependent protein kinase A.
Imagawa
M
M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093.
Chiu
R
R
Karin
M
M
D000818:Animals; D001665:Binding Sites; D002468:Cell Physiological Phenomena; D002477:Cells / Q000145:classification; D000242:Cyclic AMP / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005809:Genes, Regulator; D005814:Genes, Viral; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D014157:Transcription Factors; D008668:Metallothionein; D000242:Cyclic AMP; D011493:Protein Kinase C