Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level

Omerovic, Jasminka; Puggioni, E. M. R.; Napoletano, Silvia; Visco, Vincenzo; Fraioli, Rocco; Frati, Luigi; Gulino, Alberto; Alimandi, Maurizio

doi:10.1016/j.yexcr.2003.12.002

Cited by 89 publications

(98 citation statements)

References 25 publications

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“…The JMa splice form can be cleaved yielding a 120 kDa extracellular soluble fragment and an 85 kDa fragment (Vecchi et al, 1996). This 85 kDa fragment can translocate into the nucleus (Ni et al, 2001), where it could be involved in transcriptional regulation (Williams et al, 2004;Komuro et al, 2004;Omerovich et al, 2004). Although little is known about the role of this fragment into the nucleus, it has been recently demonstrated that it has an important role in regulating oligodendrocytes maturation induced by NRG (Lai and Feng, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…ErbB4-JMa is susceptible to a proteolytic cleavage (Vecchi and Carpenter, 1997) resulting in a fragment of approximately 85 kDa, representing the transmembrane and cytoplasmic domains of the molecule (Vecchi et al, 1996). This 85 kDa fragment can be processed by a second membrane-localized protease and translocated into the nucleus (Ni et al, 2001), where it associates to the transcriptional co-activators YAP-65 (Komuro et al, 2004;Omerovich et al, 2004) and STAT5A (Williams et al, 2004), suggesting possible involvement in transcriptional regulation. Although the EGF-like domains of neuregulins are similar, the binding specificities and affinities are different for the various combinations of ErbB receptors.…”

Section: Introductionmentioning

confidence: 99%

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Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

et al. 2006

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Neuregulins (NRGs), and their cognate receptors (ErbBs), play essential roles in numerous aspects of neural development and adult synaptic plasticity. The goal of this study was to investigate the developmental expression profiles of these molecules during the olfactory bulb (OB) maturation. The OB is a highly organized structure with cell types and synaptic connections segregated into discrete anatomical layers. We employed a novel approach by combining single-layer microdissection at different development ages,with isoform-specific semi-quantitative RT-PCR and Western blotting to monitor layer-specific developmental profiles of these molecules and alternate splice variants. Layer and age specific regulation was observed for the ErbB4 splice variants JMa/JMb and NRG-1-β1/β2 forms. With the exception of the outermost (nerve) layer, ErbB4-JMb and NRG-1-β1 are expressed throughout the OB and their expressions decrease in the adult age in most layers. In contrast both ErbB4-JMa and NRG-1-β2 are highly expressed in the granule cell layer in the early postnatal OB. This early postnatal expression correlates with the dramatic change from radial glia to astrocytes and appearance of the bulk of granule cells occurring at this developmental stage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

et al. 2006

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“…ErbB4 first cleaved by TACE is a substrate for g-secretase that releases a soluble 80-kDa intracellular domain that can translocate into the nucleus and regulate gene transcription. The ErbB4-CYT1 isoforms contain a 16-amino acid peptide with a PY motif that can be recognized by WW domains (Omerovic et al, 2004). There are two additional PY motifs in ErbB4-CYT1 isoforms (Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

“…There are two additional PY motifs in ErbB4-CYT1 isoforms (Figure 1a). Several WW domains containing proteins, including WWOX (Aqeilan et al, 2005), YAP (Komuro et al, 2003;Omerovic et al, 2004) and AIP4/Itch (Omerovic et al, 2007), have been reported to bind to ErbB4 through these PY motifs.…”

Section: Introductionmentioning

confidence: 99%

WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer

Zhou

Alimandi

et al. 2009

Oncogene

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ErbB4, a member of the epidermal growth factor receptor family, plays a role in normal breast and breast cancer development by regulating mammary epithelial cell proliferation, survival and differentiation. In this study, we show that WWP1, a C2-WW-HECT type E3 ubiquitin ligase, binds, ubiquitinates and destructs ErbB4-CYT1, but much less efficiently for CYT2, isoforms (both JMa and JMb). The protein-protein interaction occurs primarily between the first and third WW domains of WWP1 and the second PY motif of ErbB4. Knockdown of WWP1 by two different small interfering RNAs increases the endogenous ErbB4 protein levels in both MCF7 and T47D breast cancer cell lines. In addition, overexpression of the wild type, but not the catalytic inactive WWP1, dramatically decreases the endogenous ErbB4 protein levels in MCF7. Importantly, we found that WWP1 negatively regulates the heregulin-b1-stimulated ErbB4 activity as measured by the serum response element report assay and the BRCA1 mRNA expression. After a systematic screening of all WWP1 family members by small interfering RNA, we found that AIP4/Itch and HECW1/NEDL1 also negatively regulate the ErbB4 protein expression in T47D. Interestingly, the protein expression levels of both WWP1 and ErbB4 are higher in estrogen receptor-a-positive than in estrogen receptor-anegative breast cancer cell lines. These data suggest that WWP1 and its family members suppress the ErbB4 expression and function in breast cancer.

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“…This region includes a putative WW domain binding sequence that begins at Pro1053 (PPAY) as well as a putative ErbB4 phosphorylation site (Tyr1056) that has been reported to bind the SH2 domain of the regulatory subunit of PI3 kinase [7][8][9]. Thus, the CT-a and CT-b isoforms may be quite different with respect to coupling to downstream signaling events and biological responses.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines

Gallo

Bryant

Fry

et al. 2006

Biochemical and Biophysical Research Communications

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Correspondence to: David J. Riese II, Purdue Cancer Research Center, 201 S. University Street, West Lafayette, Indiana, 47907-2064, Tel (765) FAX (765) We have previously demonstrated that the constitutively-active Q646C mutant of the ErbB4 receptor tyrosine kinase inhibits colony formation by human prostate tumor cell lines. Here we use ErbB4 mutants to identify ErbB4 functions critical for inhibiting colony formation. A derivative of ErbB4 Q646 that lacks kinase activity fails to inhibit colony formation by prostate tumor cells. Likewise, an ErbB4 Q646C mutant in the context of the CT-b splicing isoform fails to inhibit colony formation. Mutation of tyrosine 1056 to phenylalanine abrogates inhibition of colony formation whereas an ErbB4 mutant that lacks all of the putative sites of tyrosine phosphorylation except for tyrosine 1056 still inhibits colony formation. Given that tyrosine 1056 is missing in the CT-b isoform, these results suggest that phosphorylation of tyrosine 1056 is critical for function. Indeed, an ErbB4 mutant that lacks kinase activity but has a glutamate phosphomimic residue substituted for tyrosine 1056 inhibits colony formation. Finally, one-dimensional phosphopeptide mapping indicates that ErbB4 Q646C is phosphorylated on tyrosine 1056. These data suggest that phosphorylation of ErbB4 tyrosine 1056 is critical for coupling ErbB4 to prostate tumor suppression.

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Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level

Cited by 89 publications

References 25 publications

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer

Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines

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