Clathrin mediates endocytosis of progastrin and activates MAPKs: role of cell surface annexin A2

Sarkar, Shubhashish; Kantara, Carla; Singh, Pomila

doi:10.1152/ajpgi.00406.2011

Cited by 17 publications

(19 citation statements)

References 71 publications

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“…Interestingly, we found that CPZ, which has been reported to impair p38 MAPK activity (14), selectively decreases LPS-induced IL-6 production in cultured macrophages, and also inhibits LPS-induced Arid5a expression. It has been also reported that p38 is critical for IL-6 production in MEFs under IL-1β signaling (15).…”

Section: Discussionmentioning

confidence: 70%

“…S1C). Recently, CPZ has been reported to inhibit p38 signaling (14). Moreover, p38 signaling has been shown to be involved in IL-6 mRNA stability (15).…”

Section: Resultsmentioning

confidence: 99%

“…In the course of our studies on the mechanism of CPZ-induced inhibition of IL-6, we found a unique molecule, AT-rich interactive domain-containing protein 5A (Arid5a), which binds to the 3′ UTR of IL-6 mRNA, and its expression is inhibited by CPZ. Interestingly, CPZ is also known to inhibit the activity of p38 MAPK (14). It has been also shown that p38 MAPK is involved in the stabilization of IL-6 mRNA via multiple AU-rich elements in the 3′ UTR of IL-6 mRNA (15).…”

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confidence: 99%

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Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo

Masuda

Ripley

Nishimura

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

189

254

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Posttranscriptional regulation of IL-6 has been largely uncharacterized, with the exception of the ribonuclease Regnase-1, which prevents autoimmunity by destabilizing IL-6 mRNA. Here, we identified AT-rich interactive domain-containing protein 5A (Arid5a) as a unique RNA binding protein, which stabilizes IL-6 but not TNF-α mRNA through binding to the 3′ untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1β, and IL-6. Arid5a deficiency inhibited elevation of IL-6 serum level in LPStreated mice and suppressed IL-6 levels and the development of T H 17 cells in experimental autoimmune encephalomyelitis. Importantly, Arid5a inhibited the destabilizing effect of Regnase-1 on IL-6 mRNA. These results indicate that Arid5a plays an important role in promotion of inflammatory processes and autoimmune diseases.immune regulation | RNA-protein complex

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Section: Discussionmentioning

confidence: 70%

“…S1C). Recently, CPZ has been reported to inhibit p38 signaling (14). Moreover, p38 signaling has been shown to be involved in IL-6 mRNA stability (15).…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo

Masuda

Ripley

Nishimura

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

189

254

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“…17 Indeed, the identity of a progastrin receptor remains an issue of intense investigation. Recent studies have suggested that Annexin A2, 32,33 ferric ions, 34 and charged glycosaminoglycans 17 are involved.…”

Section: Discussionmentioning

confidence: 99%

Progastrin-Induced Secretion of Insulin-Like Growth Factor 2 From Colonic Myofibroblasts Stimulates Colonic Epithelial Proliferation in Mice

et al. 2013

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BACKGROUND & AIMS Many colon cancers produce the hormone progastrin, which signals via autocrine and paracrine pathways to promote tumor growth. Transgenic mice that produce high circulating levels of progastrin (hGAS) have increased proliferation of colonic epithelial cells and are more susceptible to colon carcinogenesis than control mice. We investigated whether progastrin affects signaling between colonic epithelial and myofibroblast compartments to regulate tissue homeostasis and cancer susceptibility. METHODS Colonic myofibroblast numbers were assessed in hGAS and C57BL/6 mice by immunohistochemistry. Human CCD18Co myofibroblasts were incubated with recombinant human progastrin (rhPG)(1–80) for 18 hours, and proliferation was assessed in the presence of pharmacologic inhibitors. The proliferation of human HT29 colonic epithelial cells was assessed after addition of conditioned media from CCD18Co cells incubated with progastrin. The effects of the insulin-like growth factor (IGF)-I receptor antagonist AG1024 were investigated in cultured HT29 cells and on the colonic epithelium of hGAS mice compared with mice that did not express transgenic progastrin (controls). RESULTS The colonic mucosa of hGAS mice contained greater numbers of myofibroblasts that expressed α–smooth muscle actin and vimentin than controls. Incubation of CCD18Co myofibroblasts with 0.1 nmol/L rhPG(1–80) increased their proliferation, which required activation of protein kinase C and phosphatidylinositol-3 kinase. CCD18Co cells secreted IGF-II in response to rhPG(1–80), and conditioned media from CCD18Co cells that had been incubated with rhPG(1–80) increased the proliferation of HT29 cells. The colonic epithelial phenotype of hGAS mice (crypt hyperplasia, increased proliferation, and altered proportions of goblet and enteroendocrine cells) was inhibited by AG1024. CONCLUSIONS Progastrin stimulates colonic myofibroblasts to release IGF-II, which increases proliferation of colonic epithelial cells. Progastrin might therefore alter colonic epithelial cells via indirect mechanisms to promote neoplasia.

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“…43 Cell-surface ANXA2 is required for the binding and internalization of progastrin in intestinal cells, potentially by clathrin-mediated endocytosis. 44 Intracellularly, ANXA2 is present on the plasma membrane and early endosome and interacts with actin to act as a regulator of membra-cytoskeleton dynamics. [45][46][47] It was reported that ANXA2 is involved in the phagocytosis of the shed photoreceptor outer segment by pigment epithelial cells in the retina.…”

Section: Discussionmentioning

confidence: 99%

Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

Yamashita

Nagai

Toyokuni

2015

Laboratory Investigation

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Asbestos-induced mesothelioma is a worldwide problem. Parietal mesothelial cells internalize asbestos fibers that traverse the entire lung parenchyma, an action that is linked to mesothelial carcinogenesis. Thus far, vitronectin purified from serum reportedly enhances the internalization of crocidolite by mesothelial cells via integrin avb5. To reveal another mechanism by which mesothelial cells endocytose (phagocytose) asbestos, we first evaluated the effects of serum on asbestos uptake, which proved to be nonessential. Thereafter, we undertook a study to identify proteins on the surface of mesothelial cells (MeT5A) that act as receptors for asbestos uptake based on the assumption that receptors bind to asbestos with physical affinity. To this end, we incubated the membrane fraction of MeT5A cells with crocidolite or chrysotile and evaluated the adsorbed proteins using sodium dodecyl sulfate polyacrylamide gel analysis. Next, we extensively identified the proteins using an in-solution or in-gel digestion coupled with mass spectrometry. Among the identified proteins, annexin A2 (ANXA2) and transferrin receptor protein 1 (TFRC) were distinguished because of their high score and presence at the cell surface. Crocidolite uptake by MeT5A cells was significantly decreased by shRNA (short hairpin RNA)-induced knockdown of ANXA2 and direct blockade of cell surface ANXA2 using anti-ANXA2 antibody. In addition, abundant ANXA2 protein was present on the cell membrane of mesothelial cells, particularly facing the somatic cavity. These findings demonstrate that ANXA2 has a role in the mesothelial phagocytosis of crocidolite and may serve as its receptor.

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Clathrin mediates endocytosis of progastrin and activates MAPKs: role of cell surface annexin A2

Cited by 17 publications

References 71 publications

Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo

Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo

Progastrin-Induced Secretion of Insulin-Like Growth Factor 2 From Colonic Myofibroblasts Stimulates Colonic Epithelial Proliferation in Mice

Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

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