Molecular cloning, tissue-specific expression, and chromosomal localization of a novel nerve growth factor-regulated G-protein- coupled receptor, nrg-1. Mol Cell Neurosci 1999 Aug;14(2):141-52
Date
10/26/1999Pubmed ID
10532805DOI
10.1006/mcne.1999.0776Scopus ID
2-s2.0-0032877398 (requires institutional sign-in at Scopus site) 67 CitationsAbstract
A novel and differentially expressed gene, named nrg-1, was identified by EST expression profiling and subsequently isolated as a 2.2-kb full-length clone from a rat PC12 cell cDNA library. Sequence analysis reveals that nrg-1 encodes a putative seven transmembrane spanning domain protein with structural features characteristic of receptors belonging to the G-protein-coupled receptor gene superfamily. The 400-amino-acid protein encoded by nrg-1 exhibits a high degree of sequence identity (40-44%) to the Edg receptor family; members include Edg-1, Edg-2, Edg-3, Edg-4, and H218. Both Northern analysis andEST expression profiling revealed that whole-tissue distribution of nrg-1 mRNA is restricted, found almost exclusively in brain. Transcripts of nrg-1 could be ubiquitously detected in different regions, with very prominent expression in lower brain regions such as the midbrain, pons,medulla, and spinal cord. In PC12 cells, nerve growth factor induces neuronal differentiation and repressed expression of nrg-1. Two other agents that differentiate PC12 cells, fibroblast growth factor and dibdutyryl cAMP, down-regulated nrg-1 mRNA levels. Epidermal growth factor, and agent that does not induce differentiation, did not repress nrg-1 mRNA levels. In a PC12 cell mutant that is deficient in protein kinase A activity (AB.11), all three differentiating agents were unable to down-regulate nrg-1 mRNA. Hence, protein kinase A appears to be an obligatory cellular component in nrg-1 mRNA regulation. Chromosomal mapping employing a rat somatic cell readiation hybrid panel demonstrated that nrg-1 is linked to marker D8Rat54 and tightly associated with H218 on chromosome 8.
Author List
Glickman M, Malek RL, Kwitek-Black AE, Jacob HJ, Lee NHAuthor
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Base Sequence
Brain
Chromosome Mapping
Cloning, Molecular
Epidermal Growth Factor
Expressed Sequence Tags
Female
GTP-Binding Proteins
Gene Expression Regulation
Glycoproteins
Humans
Immediate-Early Proteins
Male
Molecular Sequence Data
Nerve Growth Factors
Neuregulins
Organ Specificity
PC12 Cells
RNA, Messenger
Rats
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Receptors, Lysophospholipid
Sequence Alignment
Sequence Homology, Amino Acid
Spinal Cord
Transcription, Genetic