Activation of the mitogen-activated protein kinase pathway induces transcription of the PAC-1 phosphatase gene
- Author(s)
- Grumont, RJ; Rasko, JEJ; Strasser, A; Gerondakis, S;
- Details
- Publication Year 1996-06-01,Volume 16,Issue #6,Page 2913-2921
- Journal Title
- MOLECULAR AND CELLULAR BIOLOGY
- Publication Type
- Journal Article
- Abstract
- PAC-1, an early-response gene originally identified in activated T cells, encodes a dual-specificity mitogen-activated protein kinase phosphatase. sere we report on the regulation of PAC-1 expression in murine hemopoietic cells. PAC-1 mRNA levels rapidly increase in mitogen-stimulated lymphocytes, with the induced expression being transient in B cells but sustained in activated T cells. Transfection analysis of murine PAC-1 promoter-reporter constructs established that in T cells, sequences necessary for basal and induced transcription reside within a 200-bp region located immediately upstream of the transcription initiation sites. Basal transcription is regulated in part by an E-box element that binds a 53-kDa protein. PAC-1 transcription induced by phorbol myristate acetate stimulation and the expression of the v-ras or v-raf oncogene is mediated via the E-box moth and an AP-2-related site and coincides with increased binding activity of the constitutive 53-kDa E-box-binding protein and induced binding of AP-2. The ability of an interfering ERK-2 mutant to block phorbol myristate acetate and v-ras-dependent PAC-1 transcription indicates that mitogen-activated protein kinase activation is necessary for these stimuli to induce transcription of the PAC-1 gene in T cells.
- Publisher
- AMER SOC MICROBIOLOGY
- Keywords
- SIGNAL-TRANSDUCTION PATHWAYS; IMMEDIATE-EARLY GENE; C-REL TRANSCRIPTION; FACTOR AP-2; MAP KINASE; TYROSINE-PHOSPHATASE; ENCODED PROTEIN; T-CELLS; B-CELLS; ENHANCER
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Creation Date: 1996-06-01 12:00:00