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J. Biol. Chem., Vol. 282, Issue 22, 16401-16412, June 1, 2007

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XB130, a Novel Adaptor Protein for Signal Transduction^*

Jing Xu¹, Xiao-Hui Bai¹, Monika Lodyga, Bing Han, Helan Xiao, Shaf Keshavjee, Jim Hu, Haibo Zhang^¶, Burton B. Yang^||, and Mingyao Liu²

From the Division of Cellular and Molecular Biology, University Health Network Toronto General Research Institute, Toronto, Ontario M5G 1L7, Canada, the Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, the ^¶St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada, and the ^||Sunnybrook Health Sciences Center, Toronto, Ontario M4N 3M5, Canada

Adaptor proteins are important mediators in signal transduction. In the present study, we report the cloning and characterization of a novel adaptor protein, XB130. This gene is located on human chromosome 10q25.3 and encodes a protein of 818 amino acids. It contains several Src homology (SH)2- and SH3-binding motifs, two pleckstrin homology domains, a coiled-coil region, and a number of potential tyrosine or serine/threonine phosphorylation sites. Endogenous XB130 interacts with c-Src tyrosine kinase. Their co-expression in COS-7 cells resulted in activation of c-Src and elevated tyrosine phosphorylation of multiple proteins, including XB130 itself. XB130 expression in HEK293 cells enhanced serum response element- and AP-1-dependent transcriptional activation mediated by c-Src. XB130N, an N-terminal deletion mutant lacking a putative SH3-binding motif and several putative SH2-binding sites, reduced its ability to mediate Src signal transduction. Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3, and altered cell cycles in human lung epithelial cells. These data suggest that XB130 as an adaptor may play an important role in the regulation of signal transduction and cellular functions.

Received for publication, February 26, 2007 , and in revised form, March 26, 2007.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) 442952.

^* This work was supported by Operating Grants MT-13270 and MOP-42546 from the Canadian Institutes of Health Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2, Table S1, and data.

¹ Both authors contributed equally to this study.

² To whom correspondence should be addressed: University Health Network Toronto General Hospital, Rm. TMDT 2-814, 101 College St., Toronto, Ontario M5G 1L7, Canada. Tel.: 416-581-7501; Fax: 416-581-7504; E-mail: mingyao.liu{at}utoronto.ca.

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