2005
DOI: 10.1074/jbc.m408804200
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ADAM10 Mediates Ectodomain Shedding of the Betacellulin Precursor Activated by p-Aminophenylmercuric Acetate and Extracellular Calcium Influx

Abstract: Betacellulin belongs to the family of epidermal growth factor-like growth factors that are expressed as transmembrane precursors and undergo proteolytic ectodomain shedding to release a soluble mature growth factor. In this study, we investigated the ectodomain shedding of the betacellulin precursor (pro-BTC) in conditionally immortalized wild-type (WT) and ADAM-deficient cell lines. Sequential ectodomain cleavage of the predominant cell-surface 40-kDa form of pro-BTC generated a major (26 -28 kDa) and two min… Show more

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Cited by 98 publications
(109 citation statements)
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“…We next tested whether iRhom2 also controls activated shedding of other EGFR ligands (3)(4)(5)27). The PMA-stimulated shedding of the ADAM17 substrates and EGFR ligands amphiregulin and epiregulin (4,5) was also strongly reduced in iRhom2 −/− mEFs compared with WT controls (Fig.1 E and F).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…We next tested whether iRhom2 also controls activated shedding of other EGFR ligands (3)(4)(5)27). The PMA-stimulated shedding of the ADAM17 substrates and EGFR ligands amphiregulin and epiregulin (4,5) was also strongly reduced in iRhom2 −/− mEFs compared with WT controls (Fig.1 E and F).…”
Section: Resultsmentioning
confidence: 99%
“…S1B). Moreover, the ionomycinstimulated shedding of the ADAM10 substrates and EGFR ligands betacellulin (BTC) and EGF (4,15,27) was normal in iRhom2 −/− mEFs ( Fig.1 H and I), arguing against a role of iRhom2 in ADAM10-dependent protein ectodomain shedding.…”
Section: Resultsmentioning
confidence: 99%
“…Unlike HB-EGF, Betacellulin (BTC) shedding is mediated by ADAM10 (Sahin et al, 2004) and ionomycin-induced calcium influx can stimulate ADAM10-depedent shedding (Sanderson et al, 2005;Horiuchi et al, 2007). Therefore, we Figure 1.…”
Section: Resultsmentioning
confidence: 99%
“…Such an effect might be due to the fact that those neurosteriods are sigma-1 receptor agonists (Maurice et al, 2006;Dong et al, 2009;Hayashi and Su, 2010) and activation of the sigma-1 receptor resulted in a bipolar modulation of calcium homeostasis in cell and high concentration of agonist could inhibit the free Ca 2+ in cell (Hayashi et al, 2000;Maurice et al, 2006). Since ADAM10 function is induced by free Ca 2+ in cell (Sanderson et al, 2005;Horiuchi et al, 2007), such inhibition could thus inhibit ADAM10-dependent BTC shedding. On the other hand, although sigma-1 receptor agonists could activate PKC (Fu et al, 2010;Yoon et al, 2010) which can in turn activate ADAM17-dependent shedding (Zheng et al, 2002(Zheng et al, , 2004Sahin et al, 2004), such an effect might be covered by the Figure 3.…”
Section: Discussionmentioning
confidence: 99%
“…Cite this article as Cold Spring Harb Perspect Biol 2014;6:a008995 bol esters, but can be activated by calcium ionophores, calmodulin inhibition, and the metalloprotease-activating drug p-aminophenylmercuric acetate (Sanderson et al 2005;Horiuchi et al 2007a). More physiologically, activation of purinergic receptors can also trigger ADAM 10 activity (Le Gall et al 2009), as can GPCRs (Lemjabbar and Basbaum 2002).…”
Section: Rtk Ligand Processingmentioning
confidence: 99%