JNK-interacting protein 1 promotes Akt1 activation.
Members of the JNK pathway are organized together by virtue of interactions with JNK interacting protein 1 (JIP1), a scaffold protein. Here we have investigated the possibility that JIP1 may also affect the catalytic activity of Akt1, a serine/threonine kinase that has been implicated in multiple cellular processes, including survival and proliferation. JIP1 expression enhanced Akt1 kinase activity in a dose-dependent manner following serum starvation in 293 cells. Cellular activation of Akt1 following stimulation with low concentrations of insulin-like growth factor (IGF-1) was elevated in the presence of JIP1. JIP1 expression also prolonged Akt1 stimulation after a short IGF-1 pulse. The mechanism of JIP1-mediated Akt1 activation involved JIP1 protein binding to the Akt1 pleckstrin homology domain, which in turn promoted the phosphorylation of the activation T-loop of Akt1 by phosphoinositide-dependent kinase-1. These results suggest that, in certain cellular contexts, JIP1 may act as an Akt1 scaffold, which regulates the enzymatic activity of Akt1. This study also indicates that JIP1 expression can exert signaling effects independent of JNK activity.
Kim
Albert H
AH
Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Sasaki
Takehiko
T
Chao
Moses V
MV
D064413:3-Phosphoinositide-Dependent Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D004789:Enzyme Activation; D006801:Humans; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D064413:3-Phosphoinositide-Dependent Protein Kinases; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C490666:MAPK8IP1 protein, human; C494918:AKT1 protein, human