SARA is dispensable for functional TGF‐β signaling

Bakkebø, Maren; Huse, Kanutte; Hilden, Vera; Forfang, Lise; Myklebust, June Helen; Smeland, Erlend B.; Oksvold, Morten P.

doi:10.1016/j.febslet.2012.07.027

Cited by 31 publications

(25 citation statements)

References 28 publications

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“…4 -6) is similar to the previous observations in other types of cells including HeLa cells, HepG2 cells, and Mv1Lu cells (28,30,31), although some discrepant results on the necessity of SARA for ALK5/Smad2/3 signaling were reported (42,43). Either PI3K-C2␣ depletion (ϳ80ϳ90%) or the expression of the kinase-deficient C␣ mutant strongly sup- pressed the internalization of TGF␤ receptor, like the dynamin inhibitor dynasore (Fig.…”

Section: Discussionsupporting

confidence: 87%

Phosphatidylinositol 3-Kinase Class II α-Isoform PI3K-C2α Is Required for Transforming Growth Factor β-induced Smad Signaling in Endothelial Cells

Aki

Yoshioka

Okamoto

et al. 2015

Journal of Biological Chemistry

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Background: TGF␤ receptor signals through Smad phosphorylation, which is dependent on endocytosis of TGF␤ receptors and the Smad anchor protein SARA localized on endosomes. Results: Class II PI3K-C2␣ is necessary for TGF␤ receptor endocytosis into SARA-containing endosomes, SARA-Smad complex formation, and Smad phosphorylation. Conclusion: PI3K-C2␣ serves endosomal TGF␤ receptor signaling. Significance: PI3K-C2␣ is a key molecule that is generally engaged in endosomal receptor signaling.

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Section: Discussionsupporting

confidence: 87%

Phosphatidylinositol 3-Kinase Class II α-Isoform PI3K-C2α Is Required for Transforming Growth Factor β-induced Smad Signaling in Endothelial Cells

Aki

Yoshioka

Okamoto

et al. 2015

Journal of Biological Chemistry

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“…Finally, although highly controversial (Bakkebø et al, 2012;Runyan et al, 2012), SARA has been reported to be important for activation of the TGFβ signaling pathway (Tsukazaki et al, 1998;Itoh et al, 2002). Whether this functional aspect of SARA plays a role in L1 surface expression remains to be investigated.…”

Section: Sara Regulates the Surface Expression Of L1mentioning

confidence: 99%

SARA regulates neuronal migration during neocortical development through L1 trafficking

et al. 2016

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Emerging evidence suggests that endocytic trafficking of adhesion proteins plays a crucial role in neuronal migration during neocortical development. However, molecular insights into these processes remain elusive. Here, we study the early endosomal protein Smad anchor for receptor activation (SARA) in the developing mouse brain. SARA is enriched at the apical endfeet of radial glia of the neocortex. Although SARA knockdown did not lead to detectable neurogenic phenotypes, SARA-suppressed neurons exhibited impaired orientation and migration across the intermediate zone. Mechanistically, we show that SARA knockdown neurons exhibit increased surface expression of the L1 cell adhesion molecule. Neurons ectopically expressing L1 phenocopy the migration and orientation defects caused by SARA knockdown and display increased contact with neighboring neurites. L1 knockdown effectively rescues SARA suppressioninduced phenotypes. SARA knockdown neurons eventually overcome their migration defect and enter later into the cortical plate. Nevertheless, these neurons localize at more superficial cortical layers than their control counterparts. These results suggest that SARA regulates the orientation, multipolar-to-bipolar transition and the positioning of cortical neurons via modulating surface L1 expression.

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“…Currently, a critical role for SARA in recruitment of Smad2/3 to the to the TGF-␤ receptor is controversial (70). However, mutations in SARA have been detected in ϳ33% of colon cancers (71,72).…”

Section: Cdx1 and Cdx2 Act As Tumor Suppressors-aberrantmentioning

confidence: 99%