ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily.
Using differential display of rat fetal and postnatal cardiomyocytes, we have identified a novel seven-transmembrane receptor, ETL. The cDNA-predicted amino acid sequence of ETL indicated that it encodes a 738-aa protein composed of a large extracellular domain with epidermal growth factor (EGF)-like repeats, a seven-transmembrane domain, and a short cytoplasmic tail. ETL belongs to the secretin family of G-protein-coupled peptide hormone receptors and the EGF-TM7 subfamily of receptors. The latter are characterized by a variable number of extracellular EGF and cell surface domains and conserved seven transmembrane-spanning regions. ETL mRNA expression is up-regulated in the adult rat and human heart. In situ hybridization analyses revealed expression in rat cardiomyocytes and abundant expression in vascular and bronchiolar smooth muscle cells. In COS-7 cells transfected with Myc-tagged rat ETL, rat ETL exists as a stable dimer and undergoes endoproteolytic cleavage of the extracellular domain. The proteolytic activity can be abolished by a specific mutation, T455A, in this domain. In transfected mammalian cells, ETL is associated with cell membranes and is also observed in cytoplasmic vesicles. ETL is the first seven-transmembrane receptor containing EGF-like repeats that is developmentally regulated in the heart.
Nechiporuk
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T
Department of Human Genetics, Division of Cardiology, University of Utah, Eccles Institute of Human Genetics, Salt Lake City, Utah 84112, USA.
Urness
L D
LD
Keating
M T
MT
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D012633:Secretin / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation
C428324:ADGRL4 protein, human; D017931:DNA Primers; C486072:ETL receptor, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012633:Secretin; D004815:Epidermal Growth Factor