An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels

A. John Diamonti, Pamela M. Guy, Caryn Ivanof, Karen Wong, Colleen A Sweeney, Kermit L Carraway

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Despite numerous recent advances in our understanding of the molecular mechanisms underlying receptor tyrosine kinase down-regulation and degradation in response to growth factor binding, relatively little is known about ligand-independent receptor tyrosine kinase degradation mechanisms. In a screen for proteins that might regulate the trafficking or localization of the ErbB3 receptor, we have identified a tripartite or RBCC (RING, B-box, coiled-coil) protein that interacts with the cytoplasmic tail of the receptor in an activation-independent manner. We have named this protein Nrdp1 for neuregulin receptor degradation protein-1. Northern blotting reveals ubiquitous distribution of Nrdp1 in human adult tissues, but message is particularly prominent in heart, brain, and skeletal muscle. Nrdp1 interacts specifically with the neuregulin receptors ErbB3 and ErbB4 and not with epidermal growth factor receptor or ErbB2. When coexpressed in COS7 cells, Nrdp1 mediates the redistribution of ErbB3 from the cell surface to intracellular compartments and induces the suppression of ErbB3 and ErbB4 receptor levels but not epidermal growth factor receptor or ErbB2 levels. A putative dominant-negative form of Nrdp1 potentiates neuregulin-stimulated Erk1/2 activity in transfected MCF7 breast tumor cells. Our observations suggest that Nrdp1 may act to regulate steady-state cell surface neuregulin receptor levels, thereby influencing the efficiency of neuregulin signaling.

Original languageEnglish (US)
Pages (from-to)2866-2871
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number5
DOIs
StatePublished - Mar 5 2002

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Neuregulins
Maintenance
Receptor Protein-Tyrosine Kinases
Proteins
Epidermal Growth Factor Receptor
Cell Surface Receptors
Cytoplasmic and Nuclear Receptors
Northern Blotting
Proteolysis
Tail
Intercellular Signaling Peptides and Proteins
Myocardium
Skeletal Muscle
Down-Regulation
Breast Neoplasms
Ligands
Brain

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. / Diamonti, A. John; Guy, Pamela M.; Ivanof, Caryn; Wong, Karen; Sweeney, Colleen A; Carraway, Kermit L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 5, 05.03.2002, p. 2866-2871.

Research output: Contribution to journalArticle

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