Interaction between Erbin and a Catenin-related Protein in Epithelial Cells

Jaulin-Bastard, Fanny; Arsanto, Jean-Pierre; Bivic, André Le; Navarro, Christel; Vély, Frederic; Saito, Hiroko; Marchetto, Sylvie; Hatzfeld, Meçhthild; Santoni, Marie-Josée; Birnbaum, Daniel; Borg, Jean-Paul

doi:10.1074/jbc.m109652200

Cited by 90 publications

(73 citation statements)

References 47 publications

(78 reference statements)

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“…5B). Erbin contains three domains: an N-terminal region that contains 16 LRRs, a C-terminal PDZ domain, and a middle region that show no homology to known proteins (17)(18)(19)(20)(21)(22). Ecptopic expression of the LRR domain showed similar effect on differentiation, suggesting that the inhibitory activity was contained in this domain.…”

Section: Fig 4 Erbin Blocks the Interaction Of Ras And Rafmentioning

confidence: 76%

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Erbin Suppresses the MAP Kinase Pathway

Huang

Zang

Xiong

et al. 2003

Journal of Biological Chemistry

107

114

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We present evidence here that Erbin is a negative regulator of the Ras-Raf-Erk signaling pathway. Expression of Erbin decreases transcription of the AChR ⑀-subunit gene, an event that is mediated by Erk activation. Although it interacts with the ErbB2 C terminus through the PDZ domain, Erbin has no effect on ErbB2 tyrosine phosphorylation or binding to the adaptor proteins Shc and Grb2. In contrast, expression of Erbin greatly impairs activation of Erk, but not Akt, by ligands that activate receptor tyrosine kinases. Moreover, Erbin inhibits the Erk activation by active Ras, while it fails to do so in the presence of active Raf-1. Erbin associates with active Ras, but not inactive Ras nor Raf. Consistently, Erbin interferes with the interaction between Ras and Raf both in vivo and in vitro. Finally, overexpression of Erbin leads to inhibition of NGF-induced neuronal differentiation of PC12 cells, whereas downregulation of endogenous Erbin by specific siRNA exhibits an opposite effect. Collectively, our study has identified Erbin as a novel suppressor of the Ras signaling by disrupting the Ras-Raf interaction.Extracellular signal-regulated kinases (Erk) 1 are a subfamily of mitogen-activated protein kinases (MAPK) that play important roles in a great array of cell programs including proliferation, differentiation, and apoptosis (1, 2). As exemplified by binding to growth factors such as EGF, receptor tyrosine kinases are activated and undergo autophosphorylation on tyrosine residues (3, 4). Phosphorylated tyrosine residues recruit adaptor proteins to the plasma membrane by directly interacting with modules including Src homology 2 (SH2) or phosphotyrosine binding domain (PTB). Grb2, one of such adaptors, brings guanyl nucleotide exchange factor (SOS) to the plasma membrane in proximity with Ras and expedites exchange of GDP for GTP on Ras (5). Activated Ras (GTP-bound) then directly binds to Raf and allows the latter to be activated (1, 6). Active Raf triggers sequential activation of MEK, a MAPK kinase, and Erk, leading to phosphorylation of various regulatory proteins including nuclear transcription factors such as Elk-1 and Myc as well as many cytoplasmic proteins (7, 8).In the past, extensive efforts have been made to identify factors that participate in regulation of the Ras-Raf-Erk pathway. Several modulators have been identified that positively influence the pathway at different levels. For example, the MEK partner 1 (MP1) was isolated as a binding protein that interacts with both MEK1 and Erk1 to enhance the efficiency of Erk phosphorylation by MEK (9). A second protein is the kinase suppressor of Ras (KSR) that is believed to act as a scaffold for Raf-1, MEK, and Erk (10). The Connector enhancer of KSR (CNK) directly binds to Raf and is involved in activation of the Raf/MEK/Erk pathway (11). Sur-8 is an interesting protein that contains multiple leucine-rich repeats (LRRs) (12) and binds to both Ras and Raf-1. Although Ras can directly associates with Raf upon activation, the presence of Sur-8 increase...

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Section: Fig 4 Erbin Blocks the Interaction Of Ras And Rafmentioning

confidence: 76%

“…Erbin is a protein that was identified as a binding partner for ErbB2, delta-catenin, and ARVCF (17)(18)(19)(20)(21)(22). The 180-kDa protein contains two identifiable domains: LRR and PDZ (17,19).…”

mentioning

confidence: 99%

Erbin Suppresses the MAP Kinase Pathway

Huang

Zang

Xiong

et al. 2003

Journal of Biological Chemistry

107

114

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“…The mammalian LAP proteins Erbin and Densin180 show PDZ-mediated interactions with p120-catenins (Izawa et al, 2002a;Izawa et al, 2002b;Jaulin-Bastard et al, 2002;Laura et al, 2002), and Erbin-catenin p0071 colocalize to adherens junctions and desmosomes in cultured epithelial cells (Izawa et al, 2002b;Jaulin-Bastard et al, 2002). Disruption of Erbin-p0071 interactions leads to aberrant cell morphology and disruption of cell-cell contacts (Jaulin-Bastard et al, 2002). Similarly, Drosophila Scrib is required for proper morphology and formation of septate junctions in epithelia (Bilder and Perrimon, 2000), and we find the PDZ domains are necessary for efficient Scrib localization to the epithelial cell septate junctions.…”

Section: Scrib Lrrs Regulate Cortical Protein Localizationmentioning

confidence: 99%

Scribble protein domain mapping reveals a multistep localization mechanism and domains necessary for establishing cortical polarity

Albertson

Chabu

Sheehan

et al. 2004

Journal of Cell Science

116

117

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“…Densin-180 was first described as a neuronal-specific LAP protein linked to calmodulin kinase II and a-actinin (Walikonis et al, 2001). Erbin, a close homologue of Densin-180, has a more ubiquitous expression, and binds to the tyrosine kinase receptor ErbB2, and to p0071, a p120-catenin-related protein (Borg et al, 2000;Huang et al, 2001;Jaulin-Bastard et al, 2002;Ohno et al, 2002). Erbin and Densin-180 are homologues of LET-413 in Caenorhabditis elegans, a LAP protein required for epithelial integrity (Legouis et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Junctional recruitment of mammalian Scribble relies on E-cadherin engagement

et al. 2005

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Members of the LAP protein family, LET-413 inCaenorhabditis elegans, Scribble in Drosophila melanogaster, and Erbin, Lano, Densin-180 and hScrib in mammals, have conserved structural features. LET-413 and Scribble are junctional proteins involved in establishing and maintaining epithelial cell polarity. scribble also behaves as a neoplastic tumor suppressor gene. We show here that, in epithelial cells, hScrib is recruited at cell-cell junctions in an E-cadherin-dependent manner as shown by calcium switch assays in MDCK cells, re-expression of E-cadherin in MDA-231 cells treated by 5-Aza-2 0 -deoxycytidine (5Aza), and siRNA experiments. hScrib is restricted at the basolateral membrane of epithelial cells by its LRR domain, and is enriched in Triton X-100-insoluble fractions. In breast cancers, most lobular tumors did not express hScrib and E-cadherin while ductal tumors had a less frequent downregulation of hScrib. Our data provide additional insights on the modalities of recruitment of hScrib at the cell-cell junctions, and establish a potential link between the E-cadherin and hScrib tumor suppressors.

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Interaction between Erbin and a Catenin-related Protein in Epithelial Cells

Cited by 90 publications

References 47 publications

Erbin Suppresses the MAP Kinase Pathway

Erbin Suppresses the MAP Kinase Pathway

Scribble protein domain mapping reveals a multistep localization mechanism and domains necessary for establishing cortical polarity

Junctional recruitment of mammalian Scribble relies on E-cadherin engagement

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