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Molecular and Cellular Biology, March 1999, p. 1961-1972, Vol. 19, No. 3
Department of Biological Regulation, The
Weizmann Institute of Science, Rehovot 76100, Israel
Received 29 July 1998/Returned for modification 14 September
1998/Accepted 30 November 1998
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
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Neu Differentiation Factor Stimulates
Phosphorylation and Activation of the Sp1 Transcription
Factor
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.
*
Corresponding author. Mailing address: Department of
Biological Regulation, The Weizmann Institute of Science, Rehovot
76100, Israel. Phone: 972-8-9343974. Fax: 972-8-9344116. E-mail:
liyarden{at}weizmann.weizmann.ac.il.
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