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PMID: 10022883 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor.

Molecular and cellular biology ·Vol. 19 ·No. 3 ·1999-03-00 ·Pages 1961-72

Alroy I, Soussan L, Seger R, Yarden Y

Abstract

Neu differentiation factors (NDFs), or neuregulins, are epidermal growth factor-like growth factors which bind to two tyrosine kinase receptors, ErbB-3 and ErbB-4. The transcription of several genes is regulated by neuregulins, including genes encoding specific subunits of the acetylcholine receptor at the neuromuscular junction. Here, we have examined the promoter of the acetylcholine receptor epsilon subunit and delineated a minimal CA-rich sequence which mediates transcriptional activation by NDF (NDF-response element [NRE]). Using gel mobility shift analysis with an NRE oligonucleotide, we detected two complexes that are induced by treatment with neuregulin and other growth factors and identified Sp1, a constitutively expressed zinc finger phosphoprotein, as a component of one of these complexes. Phosphatase treatment, two-dimensional gel electrophoresis, and an in-gel kinase assay indicated that Sp1 is phosphorylated by a 60-kDa kinase in response to NDF-induced signals. Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus.

MeSH Terms
Animals DNA-Binding Proteins/metabolism Enzyme Inhibitors/pharmacology Gene Expression Regulation Glycoproteins/metabolism HeLa Cells Humans Ligands Nerve Growth Factors/genetics Neuregulins Neurotrophin 3 Okadaic Acid/pharmacology Phosphorylation Promoter Regions, Genetic Rats Receptors, Nicotinic/genetics Sp1 Transcription Factor/metabolism Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins Enzyme Inhibitors Glycoproteins Ligands Nerve Growth Factors Neuregulins Neurotrophin 3 Receptors, Nicotinic Sp1 Transcription Factor Okadaic Acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Alroy I
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Soussan L
Seger R
Yarden Y
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.3.1961
Published
1999-03-00
Pages
1961-72
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC83989
Subset
IM
Grants
NCI NIH HHS · R01 CA072981 · United States
NCI NIH HHS · R37 CA072981 · United States
NCI NIH HHS · CA-72981 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.3.1961 PMC Full Text View journal details
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