Neu Differentiation Factor Stimulates Phosphorylation and Activation of the Sp1 Transcription Factor
AUTOR(ES)
Alroy, Iris
FONTE
American Society for Microbiology
RESUMO
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 ɛ 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=83989Documentos Relacionados
- Phosphorylation of Transcription Factor Sp1 during Herpes Simplex Virus Type 1 Infection
- Oncogenic activation of p185neu stimulates tyrosine phosphorylation in vivo.
- The retinoblastoma gene product RB stimulates Sp1-mediated transcription by liberating Sp1 from a negative regulator.
- Sp1 activation of a TATA-less promoter requires a species-specific interaction involving transcription factor IID.
- Retinoid-induced apoptosis and Sp1 cleavage occur independently of transcription and require caspase activation.