Cross-talk between JIP3 and JIP1 during glucose deprivation: SEK1-JNK2 and Akt1 act as mediators.
We have previously observed that glucose deprivation activates the ASK1-MEK-MAPK signal transduction pathway. In the present study, we reveal that two scaffolding proteins, JIP1 and JIP3, have a cross-talk that leads to the regulation of the ASK1-SEK1-JNK signal during glucose deprivation. Glucose deprivation rapidly increases the interaction between ASK1 and JIP3, and the consequently activated ASK1 phosphorylates SEK1 on the Thr-261 residue. The activated SEK1 dissociates from JIP3 and phosphorylates JNK2 on the Tyr-185 residue. Phosphorylated JNK2 binds to JIP1, and the phosphorylation of the Thr-183 residue of JNK2 occurs. JNK2 phosphorylates JIP1 on the Thr-103 residue and leads to dissociation of Akt1 from JIP1. Dissociated Akt1 binds to SEK1 and ASK1 and inhibits their enzyme activity by phosphorylating SEK1 on the Ser-80 residue and ASK1 on the Ser-83 residue. Taken together, our data demonstrate that cross-talk between JIP3 and JIP1 is mediated through SEK1-JNK2 and Akt1.
Song
Jae J
JJ
Department of Surgery and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Lee
Yong J
YJ
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D020239:Receptor Cross-Talk; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C490666:MAPK8IP1 protein, human; C485750:MAPK8IP3 protein, human; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D048056:Mitogen-Activated Protein Kinase 9; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048848:MAP Kinase Kinase Kinase 5; D048670:MAP Kinase Kinase 4; D005947:Glucose