The association of the SH3 (Src homology 3) domain of SFKs (Src family kinases) with protein partners bearing proline-rich motifs has been implicated in the regulation of SFK activity, and has been described as a possible mechanism of relocalization of SFKs to subcellular compartments. We demonstrate in the present study for the first time that p13, an accessory protein encoded by the HTLV-1 (human T-cell leukaemia virus type 1), binds the SH3 domain of SFKs via its C-terminal proline-rich motif, forming a stable heterodimer that translocates to mitochondria by virtue of its N-terminal mitochondrial localization signal. As a result, the activity of SFKs is dramatically enhanced, with a subsequent increase in mitochondrial tyrosine phosphorylation, and the recognized ability of p13 to insert itself into the inner mitochondrial membrane and to perturb the mitochondrial membrane potential is abolished. Overall, the present study, in addition to confirming that the catalytic activity of SFKs is modulated by interactors of their SH3 domain, leads us to hypothesize a general mechanism by which proteins bearing a proline-rich motif and a mitochondrial localization signal at the same time may act as carriers of SFKs into mitochondria, thus contributing to the regulation of mitochondrial functions under various pathophysiological conditions.
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Research Article|
October 13 2011
Interaction between the SH3 domain of Src family kinases and the proline-rich motif of HTLV-1 p13: a novel mechanism underlying delivery of Src family kinases to mitochondria
Elena Tibaldi;
Elena Tibaldi
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Andrea Venerando;
Andrea Venerando
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
†Venetian Institute of Molecular Medicine (VIMM), Via G. Orus, 2, 35129 Padua, Italy
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Francesca Zonta;
Francesca Zonta
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Carlo Bidoia;
Carlo Bidoia
‡Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland
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Elisa Magrin;
Elisa Magrin
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Oriano Marin;
Oriano Marin
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Antonio Toninello;
Antonio Toninello
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Luciana Bordin;
Luciana Bordin
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Veronica Martini;
Veronica Martini
†Venetian Institute of Molecular Medicine (VIMM), Via G. Orus, 2, 35129 Padua, Italy
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Mario Angelo Pagano;
Mario Angelo Pagano
1
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
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Anna Maria Brunati
*Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy
2To whom correspondence should be addressed (email annamaria.brunati@unipd.it).
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Publisher: Portland Press Ltd
Received:
October 07 2010
Revision Received:
June 22 2011
Accepted:
July 07 2011
Accepted Manuscript online:
July 07 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 439 (3): 505–518.
Article history
Received:
October 07 2010
Revision Received:
June 22 2011
Accepted:
July 07 2011
Accepted Manuscript online:
July 07 2011
Citation
Elena Tibaldi, Andrea Venerando, Francesca Zonta, Carlo Bidoia, Elisa Magrin, Oriano Marin, Antonio Toninello, Luciana Bordin, Veronica Martini, Mario Angelo Pagano, Anna Maria Brunati; Interaction between the SH3 domain of Src family kinases and the proline-rich motif of HTLV-1 p13: a novel mechanism underlying delivery of Src family kinases to mitochondria. Biochem J 1 November 2011; 439 (3): 505–518. doi: https://doi.org/10.1042/BJ20101650
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