title: Mouse DTEF-1 (ETFR-1, TEF-5) is a transcriptional activator in alpha 1-adrenergic agonist-stimulated cardiac myocytes.
abstract: alpha(1)-Adrenergic signaling in cardiac myocytes activates the skeletal muscle alpha-actin gene through an MCAT cis-element, the binding site of the transcriptional enhancer factor-1 (TEF-1) family of transcription factors. TEF-1 accounts for more than 85% of the MCAT binding activity in neonatal rat cardiac myocytes. Other TEF-1 family members account for the rest. Although TEF-1 itself has little effect on the alpha(1)-adrenergic activation of skeletal muscle alpha-actin, the related factor RTEF-1 augments the response and is a target of alpha(1)-adrenergic signaling. Here, we examined another TEF-1 family member expressed in cardiac muscle, DTEF-1, and observed that it also augmented the alpha(1)-adrenergic response of skeletal muscle alpha-actin. A DTEF-1 peptide-specific antibody revealed that endogenous DTEF-1 accounts for up to 5% of the MCAT binding activity in neonatal rat cardiac myocytes. A TEF-1/DTEF-1 chimera suggests that alpha(1)-adrenergic signaling modulates DTEF-1 function. Orthophosphate labeling and immunoprecipitation of an epitope-tagged DTEF-1 showed that DTEF-1 is phosphorylated in vivo. alpha(1)-Adrenergic stimulation increased while phosphatase treatment lowered the MCAT binding by DTEF-1 and the endogenous non-TEF-1 MCAT-binding factor. In contrast, alpha(1)-adrenergic stimulation did not alter, and phosphatase treatment increased, MCAT binding of TEF-1 and RTEF-1. Taken together, these results suggest that DTEF-1 is a target for alpha(1)-adrenergic activation of the skeletal muscle alpha-actin gene in neonatal rat cardiac myocytes.
authors: Cardiovascular Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors: Tomoji
authors: T
authors: Maeda
authors: Joseph R
authors: JR
authors: Mazzulli
authors: Iain K G
authors: IK
authors: Farrance
authors: Alexandre F R
authors: AF
authors: Stewart
mesh_terms: D000199:Actins / Q000235:genetics; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000166:cytology*; D011401:Promoter Regions, Genetic; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: D000199:Actins; D000316:Adrenergic alpha-Agonists; D017931:DNA Primers; D004268:DNA-Binding Proteins; C098771:DTEF-1 protein, Gallus gallus; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D000091262:TEA Domain Transcription Factors; C106169:TEAD3 protein, human; C432156:Tead3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors