Tyrosine Phosphorylation of Grb2: Role in Prolactin/Epidermal Growth Factor Cross Talk in Mammary Epithelial Cell Growth and Differentiation

Haines, Eric; Minoo, Parham; Feng, Zhenqian; Resalatpanah, Nazila; Nie, Xin; Campiglio, Manuela; Álvarez, Laura; Cocolakis, Eftihia; Ridha, Mohammed; Fulvio, Mauricio Di; Gómez‐Cambronero, Julian; Lebrun, Jean Jacques; Ali, Suhad

doi:10.1128/mcb.00034-09

Cited by 29 publications

(25 citation statements)

References 38 publications

(56 reference statements)

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“…Previous reports suggested an inhibitory role of Grb2 Tyr 7 , Tyr 37 , Tyr 52 , and Tyr 209 phosphorylation in receptor tyrosine kinase signaling (16) (43). Instead, in our system Grb2 Tyr 160 mutation was not show to have a role in ALCL proliferation.…”

Section: Grb2 In Npm-alk Signalingcontrasting

confidence: 80%

“…Furthermore, a recent report showed a role for tyrosine phosphorylation of Grb2 in prolactin receptor/Jak2 signaling (42). In this contest, tyrosine phosphorylation of Grb2 was shown to mediate the inhibitory signals of prolactin on the Ras/MAPK pathway, thereby allowing for the prolactin antagonism of EGFinduced cell proliferation in mammary epithelial cells (43).…”

Section: Grb2 In Npm-alk Signalingmentioning

confidence: 92%

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352 Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) mediated signaling and anaplastic large cell lymphoma growth

Riera¹,

Lasorsa²,

Ambrogio³

et al. 2010

European Journal of Cancer Supplements

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Section: Grb2 In Npm-alk Signalingcontrasting

confidence: 80%

Section: Grb2 In Npm-alk Signalingmentioning

confidence: 92%

352 Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) mediated signaling and anaplastic large cell lymphoma growth

Riera¹,

Lasorsa²,

Ambrogio³

et al. 2010

European Journal of Cancer Supplements

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“…B). Dephosphorylation as the activated state of GRB2 is supported by the observation that phosphorylated GRB2 down‐regulates tyrosine kinase signaling (Fig. S3).…”

Section: Discussionmentioning

confidence: 70%

“…Testing the cellular distribution of proteins containing one or more SH3 domains in the presence and absence of SPRR2a showed that GRB2, an adaptor protein involved in RTK signal transduction, translocated from the cytoplasm to the nucleus following SPRR2a induction. SPRR2a expression also resulted in dephosphorylation of cytoplasmic GRB2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Small proline rich protein 2a in benign and malignant liver disease

et al. 2014

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STAT3-driven expression of small proline rich protein 2a (SPRR2a), which acts as an src homology 3 (SH3) domain ligand, induces biliary epithelial cell (BEC) epithelialmesenchymal transition (EMT), which, in turn, promotes wound healing. SPRR2a also quenches free radicals and protects against oxidative stress and DNA damage in nonneoplastic BEC. Sprr2a-induced EMT also increases local invasiveness of cholangiocarcinomas (CC), but prevents metastases. Understanding SPRR2a regulation of EMT has potential for therapeutic targeting in both benign and malignant liver disease. Molecular mechanisms responsible for SPRR2a-induced EMT were characterized, in vitro, and then evidence for utilization of these pathways was sought in human intrahepatic CC, in vivo, using multiplex labeling and software-assisted morphometric analysis. SPRR2a complexes with ZEB1 and CtBP on the microRNA (miR)-200c/141 promoter resulting in synergic suppression of miR-200c/141 transcription, which is required for maintenance of the BEC epithelial phenotype. SPRR2a induction promotes dephosphorylation and nuclear translocation of the SH3-domain containing protein GRB2 and an SH3-domain ligand in ZEB1 is required for SPRR2a-induced synergic suppression of miR-200c/141. Multiplex protein labeling of CC and morphometric analyses showed: 1) up-regulation of ZEB-1, and 2) down-regulation of CK19 in intrahepatic CC compared to nonneoplastic BEC, consistent with previous CC proteomic studies showing EMT during cholangiocarcinogenesis. Conclusion: SPRR2a modulates ZEB-1 signaling by way of miR-200c/141-associated EMT through SH3-domain networks and contributes to benign and malignant BEC wound-healing responses. (HEPATOLOGY 2014;59:1130-1143

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“…This protein is a regulatory subunit of signaling molecules and pathways whose activity is modulated by tyrosine receptor kinases, providing a link between cell surface growth factor receptors and the Ras signaling pathway [56,57]. Tyrosine phosphorylation of GRB2 interferes with the binding function of SH3 domains to SOS proteins, thereby negatively influencing transcription factor activation and proinflammatory responses.…”

Section: Signaling Transductionmentioning

confidence: 99%

An analysis of the phosphoproteome of immune cell lines exposed to the immunomodulatory mycotoxin deoxynivalenol

Costa

Keen

Wild

et al. 2011

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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a b s t r a c t a r t i c l e i n f oThe mycotoxin deoxynivalenol (DON) commonly contaminates cereal grains. It is ubiquitous in the Western European diet, although chronic, low-dose effects in humans are not well described, but immunotoxicity has been reported. In this study, two-dimensional gel electrophoresis was used to identify phosphoproteomic changes in human B (RPMI1788) and T (Jurkat E6.1) lymphocyte cell lines after exposure to modest concentrations of DON (up to 500 ng/mL) for 24 h. Proteins identified as having altered phosphorylation state post-treatment (C-1-tetrahydrofolate synthase, eukaryotic elongation factor 2, nucleoside diphosphate kinase A, heat shock cognate 71 kDa protein, eukaryotic translation initiation factor 3 subunit I and growth factor receptor-bound protein 2) are involved in regulation of metabolic pathways, protein biosynthesis and signaling transduction. All exhibited a greater than 1.4-fold change, reproducible in three separate experiments consisting of 36 gels in total. Flow cytometry validated the observations for eukaryotic elongation factor 2 and growth factor receptor-bound protein 2. These findings provide further insights as to how low dose exposure to DON may affect human immune function and may have potential as mechanismbased phosphoprotein biomarkers for DON exposure.

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Tyrosine Phosphorylation of Grb2: Role in Prolactin/Epidermal Growth Factor Cross Talk in Mammary Epithelial Cell Growth and Differentiation

Cited by 29 publications

References 38 publications

352 Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) mediated signaling and anaplastic large cell lymphoma growth

352 Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) mediated signaling and anaplastic large cell lymphoma growth

Small proline rich protein 2a in benign and malignant liver disease

An analysis of the phosphoproteome of immune cell lines exposed to the immunomodulatory mycotoxin deoxynivalenol

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