Interaction between the SH3 domain of Src family kinases and HTLV-1 p13's proline rich motif: a novel mechanism underlying delivery of Src family kinases to mitochondria
Résumé
The association of the SH3 domain of Src Family Kinases (SFKs) with protein partners bearing proline rich motifs has been implicated in the regulation of the activity, and recently described as a possible mechanism of relocalization to subcellular compartments, of SFKs. We demonstrate for the first time that p13, an accessory protein encoded by the Human T-cell Leukemia Virus type 1 (HTLV-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 subsequent increase in mitochondrial tyrosine phosphorylation and the recognized p13's ability to insert itself into the inner mitochondrial membrane and to perturb the mitochondrial membrane potential is abolished. Overall, this study, in addition to confirming that the catalytic activity of SFKs is modulated by interactors of their SH3 domain, lead 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 regulate mitochondrial functions under various pathophysiological conditions.
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