title: 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.
abstract: 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.
authors: Department of Biological Chemistry, University of Padua, Italy.
authors: Elena
authors: E
authors: Tibaldi
authors: Andrea
authors: A
authors: Venerando
authors: Francesca
authors: F
authors: Zonta
authors: Carlo
authors: C
authors: Bidoia
authors: Elisa
authors: E
authors: Magrin
authors: Oriano
authors: O
authors: Marin
authors: Antonio
authors: A
authors: Toninello
authors: Luciana
authors: L
authors: Bordin
authors: Veronica
authors: V
authors: Martini
authors: Mario Angelo
authors: MA
authors: Pagano
authors: Anna Maria
authors: AM
authors: Brunati
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics; D055232:Proline-Rich Protein Domains; D011485:Protein Binding; D055503:Protein Multimerization / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D011817:Rabbits; D051381:Rats; D012191:Retroviridae Proteins / Q000737:chemistry* / Q000235:genetics; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry* / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D012191:Retroviridae Proteins; C072813:rof protein, Human T-lymphotropic virus 1; D019061:src-Family Kinases