TTP at Ser245 phosphorylation by AKT is required for binding to 14-3-3.
Transferrin receptor trafficking protein (TTP) is a key molecule for selective internalization of the transferrin receptor (Tf-R) through endocytic protein complexes. To identify the proteins that directly regulate TTP, we performed a yeast two-hybrid analysis and identified 14-3-3, which can modulate the activation state of target proteins. Subsequent analyses demonstrated that TTP directly binds to multiple 14-3-3 isotypes via its Ser(245) residue (Ser(246) in human) and that these proteins are associated at the plasma membrane. Ser(245) was also found to be a substrate for AKT and the resulting Ser(245) phosphorylation induced the TTP-14-3-3 interaction. Exposure to hydrogen peroxide rapidly enhanced this association in an ovarian cell line. These results suggest that TTP Ser(245) is the principal target for the modulation of this protein via the AKT signalling cascade.
Chiba
Shigeki
S
Laboratory of Molecular Cell Physiology, Faculty of Agriculture, Ehime University, 3-Tarumi, Matsuyama, Ehime 7908566, Japan.
Tokuhara
Mie
M
Morita
Eugene Hayato
EH
Abe
Shunnosuke
S
D048948:14-3-3 Proteins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013379:Substrate Specificity / Q000187:drug effects
D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D020033:Protein Isoforms; C541099:TTP protein, mouse; D010768:Phosphoserine; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt