Tyrosine Dephosphorylation of the Syndecan-1 PDZ Binding Domain Regulates Syntenin-1 Recruitment

Sulka, Béatrice; Lortat‐Jacob, Hugues; Terreux, Raphaël; Letourneur, François; Rousselle, Patricia

doi:10.1074/jbc.m807643200

Cited by 52 publications

(57 citation statements)

References 58 publications

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“…An alternative possibility is that the interaction between the syndecan and the integrin is not direct but is mediated by a PDZ-domain protein, such as syntenin. This possibility would seemingly be supported by recent work showing that Sdc1 binding to syntenin is promoted upon epithelial cells binding to the LG4,5 domain of LN332 (39). However, silencing syntenin expression in the A431 cells with RNA interference has no effect on the integrin signaling mechanism.…”

Section: Tsupporting

confidence: 58%

“…Engagement of LG4,5 enhances keratinocyte cell spreading and migration (36 -38), which probably traces to Sdc1 because of its high expression on keratinocytes. Interestingly, it is proposed that this is regulated by phosphorylation of the C2 region of the syndecan cytoplasmic domain and its interaction with the PDZ domain of syntenin (39). In addition, Sdc1 has been shown to interact with the ␥2 chain of LN332 (40).…”

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confidence: 99%

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Interaction of Syndecan and α6β4 Integrin Cytoplasmic Domains

Wang

Leavitt

Ramaswamy

et al. 2010

Journal of Biological Chemistry

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The ␣6␤4 integrin is a laminin 332 (LN332) receptor central to the formation of hemidesmosomes in epithelial layers. However, the integrin becomes phosphorylated by keratinocytes responding to epidermal growth factor in skin wounds or by squamous cell carcinomas that overexpress/hyperactivate the tyrosine kinase ErbB2, epidermal growth factor receptor, or c-Met. We show here that the ␤4-dependent signaling in A431 human squamous carcinoma cells is dependent on the syndecan family of matrix receptors. Yeast two-hybrid analysis identifies an interaction within the distal third (amino acids 1473-1752) of the ␤4 cytoplasmic domain and the conserved C2 region of the syndecan cytoplasmic domain. Via its C2 region, Sdc1 forms a complex with the ␣6␤4 integrin along with the receptor tyrosine kinase ErbB2 and the cytoplasmic kinase Fyn in A431 cells. Engagement of LN332 or clustering of the ␣6␤4 integrin with integrin-specific antibodies causes phosphorylation of ErbB2, Fyn, and the ␤4 subunit as well as activation of phosphatidylinositol 3-kinase and Akt and their assimilation into this complex. This leads to phosphatidylinositol 3-kinase-dependent cell spreading and Akt-dependent protection from apoptosis. This is disrupted by RNA interference silencing of Sdc1 but can be rescued by mouse Sdc1 or Sdc4 but not by syndecan mutants lacking their C-terminal C2 region. This disruption does not prevent the phosphorylation of ErbB2 or Fyn but blocks the Fynmediated phosphorylation of the ␤4 tail. We propose that syndecans engage the distal region of the ␤4 cytoplasmic domain and bring it to the plasma membrane, where it can be acted upon by Src family kinases.The ␣6␤4 integrin is a laminin 332 (LN332, 2 also known as LN5 or kalinin) receptor that forms hemidesmosomes in epithelial cells (reviewed in Refs. 1-4). It engages LN332 linked to collagen VII anchoring fibrils in the extracellular matrix (5) and simultaneously engages cytoplasmic proteins (e.g. plectin and BP230) and the transmembrane protein BP180 via the long (ϳ1,000-amino acid) cytoplasmic domain of the ␤4 integrin subunit. These cytoplasmic interactions involve two pairs of fibronectin type III (FNIII) repeats in the ␤4 tail and the connecting segment joining these pairs. This couples the integrin to the intermediate filament cytoskeleton and provides a stable anchorage that resists frictional forces on the epithelium.In contrast to this stabilizing role of the ␣6␤4 integrin, phosphorylation of the ␤4 cytoplasmic domain causes hemidesmosome disassembly and activation of ␣6␤4 signaling. Skin wounding causes relocalization of the integrin to lamellipodia of invading keratinocytes in response to EGF or macrophagestimulating factor (6). In tumor cells, overexpression of the integrin or overexpression and/or hyperactivation of the receptor tyrosine kinase c-Met (hepatocyte growth factor receptor), ErbB1 (EGFR), or ErbB2 causes phosphorylation of the integrin and promotes the proliferation, survival, and invasion of the tumor cells (7-9). The sites targeted by these kin...

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Section: Tsupporting

confidence: 58%

mentioning

confidence: 99%

Interaction of Syndecan and α6β4 Integrin Cytoplasmic Domains

Wang

Leavitt

Ramaswamy

et al. 2010

Journal of Biological Chemistry

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“…Where information is available, key differences are seen between Sdc1 engaging the ␤4 integrin, syntenin, and Tiam-1. Binding to syntenin relies on an XFXA motif and is disrupted if Tyr (P Ϫ1 ) is phosphorylated (54,55,70). Binding to the Tiam-1 PDZ domain appears to rely on KXEXFXX composed partly of the C2 region (EFYA) and KXE from the syndecan V region.…”

Section: Blotmentioning

confidence: 99%

“…Note that the EFYA sequence that comprises the C2 region has been shown to be a PDZ domainbinding motif, depending on Phe (P Ϫ2 ) and Ala (P 0 ) (54). Tyr at P Ϫ1 can be mutated to Phe or Ala, but it cannot be phosphorylated without disrupting PDZ domain binding (54,55). To test whether ␤4 integrin binding obeys these same rules, we tested peptides in which the Phe or Tyr is mutated, or Tyr is phosphor- …”

Section: Syndecans Regulate Her2-/egfr-specific Integrin Activationmentioning

confidence: 99%

Cytoplasmic Domain Interactions of Syndecan-1 and Syndecan-4 with α6β4 Integrin Mediate Human Epidermal Growth Factor Receptor (HER1 and HER2)-dependent Motility and Survival

Wang

Jin

Beauvais

et al. 2014

Journal of Biological Chemistry

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Background: The ␣6␤4 integrin assembles via an unknown mechanism with receptor tyrosine kinases. Results: HER2-dependent activation of ␣6␤4 depends on capture of the ␤4 cytoplasmic domain by syndecan-1, whereas HER1 (EGFR) relies on syndecan-4. Conclusion: Cell invasion and survival mediated by the ␣6␤4 integrin depend on its assembly with kinase-specific syndecans. Significance: These novel interactions may provide targets for new therapeutics to combat carcinogenesis.

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“…When the cells contact with the extracellular matrix (ECM), extended filopodia binds to ECM through integrins and mediates the formation of focal adhesion, which is a power source of cell migration (Meurice et al, 2010). Mda-9/syntenin could remodel the actin cytoskeleton, induce the formation of a variety of plasma membrane structures including goffer, lamellipodia and neurite-like structure in neurons and different types of tumor cells, indicating it may play a role in tumor cell adhesion and migration (Zimmermann et al, 2001;Hirbec et al, 2005;Sulka et al, 2009). Some clinical trials have confirmed that mda-9/syntenin was overexpressed in melanoma, metastatic breast cancer and gastrointestinal tumors and the level of mda-9/syntenin was closely correlated with the tumor malignant grades and tumor metastasis (Koo et al, 2002;Helmke et al, 2004;Boukerche et al, 2005;Boukerche et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Mda-9/syntenin Promotes Human Brain Glioma Migration through Focal Adhesion Kinase (FAK)-JNK and FAK-AKT Signaling

Zhong

Ran²,

Tang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (

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Tyrosine Dephosphorylation of the Syndecan-1 PDZ Binding Domain Regulates Syntenin-1 Recruitment

Cited by 52 publications

References 58 publications

Interaction of Syndecan and α6β4 Integrin Cytoplasmic Domains

Interaction of Syndecan and α6β4 Integrin Cytoplasmic Domains

Cytoplasmic Domain Interactions of Syndecan-1 and Syndecan-4 with α6β4 Integrin Mediate Human Epidermal Growth Factor Receptor (HER1 and HER2)-dependent Motility and Survival

Mda-9/syntenin Promotes Human Brain Glioma Migration through Focal Adhesion Kinase (FAK)-JNK and FAK-AKT Signaling

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