Abstract:
:The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent mutated version of the chicken c-erbA alpha-encoded thyroid hormone receptor. The v-erbA gene product, a 75-kD gag/v-erbA fusion protein, is phosphorylated on Ser-16/17 of its v-erbA-encoded domain, and phosphorylation at this site is increased in vivo after activation of either the PKA or PKC signal transduction pathways. To test the hypothesis that phosphorylation of Ser-16/17 regulates gag/v-erbA protein function, mutant proteins in which Ser-16/17 had been changed to alanine or threonine residues were analyzed for their ability to inhibit erythroid differentiation of ts v-erbB or ts v-sea-transformed erythroblasts at nonpermissive temperature. Conversion of Ser-16/17 into alanine, although not affecting nuclear localization or DNA binding of the gag/erbA protein, prevented phosphorylation of the v-erbA-encoded domain of the protein both in unstimulated cells or after stimulation by PKA and PKC activators. The nonphosphorylatable AA-gag/v-erbA protein proved unable to inhibit temperature-induced differentiation of ts v-erbB and ts v-sea-transformed erythroblasts and to block expression of the erythrocyte-specific genes band 3 and carbonic anhydrase II. Back mutation of these alanine residues to serine resulted in the recovery of both normal phosphorylation levels and wild-type biological activity. In contrast, substitution of Ser-16/17 for threonine, which preserved phosphorylation in unstimulated cells but not PKA- and PKC-enhanced phosphorylation, resulted in a partially active gag/v-erbA protein. These results, together with the fact that the protein kinase inhibitor H7 resulted in both a dose-dependent inhibition of gag/v-erbA protein phosphorylation and the induction of terminal differentiation of AEV-transformed erythroblasts show that phosphorylation of gag/v-erbA protein is required for full biological activity. These results support the hypothesis that phosphorylation of the gag/v-erbA protein is important for transcriptional repression of at least some of its target genes in erythroid cells.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Glineur C,Zenke M,Beug H,Ghysdael Jdoi
10.1101/gad.4.10.1663subject
Has Abstractpub_date
1990-10-01 00:00:00pages
1663-76issue
10eissn
0890-9369issn
1549-5477journal_volume
4pub_type
杂志文章abstract::Many bacterial small regulatory RNAs (sRNAs) pair with mRNA targets, stimulating or inhibiting mRNA stability and/or translation. Regulation of these sRNAs is usually due to tight transcriptional regulation of synthesis.In this issue of Genes & Development and a related paper in Molecular Microbiology, Figueroa-Bossi ...
journal_title:Genes & development
pub_type: 评论,杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章,评审
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2005-04-15 00:00:00
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pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.892301
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2013-01-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.10.1504
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.773
更新日期:1991-05-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.3.383
更新日期:1997-02-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2010-05-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1800
更新日期:1988-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1999-05-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1988-07-01 00:00:00
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journal_title:Genes & development
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更新日期:2007-05-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1999-08-01 00:00:00