Akt binds to and phosphorylates phospholipase C-gamma1 in response to epidermal growth factor.
Both phospholipase (PL) C-gamma1 and Akt (protein kinase B; PKB) are signaling proteins that play significant roles in the intracellular signaling mechanism used by receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR). EGFR activates PLC-gamma1 directly and activates Akt indirectly through phosphatidylinositol 3-kinase (PI3K). Many studies have shown that the PLC-gamma1 pathway and PI3K-Akt pathway interact with each other. However, it is not known whether PLC-gamma1 binds to Akt directly. In this communication, we identified a novel interaction between PLC-gamma1 and Akt. We demonstrated that the interaction is mediated by the binding of PLC-gamma1 Src homology (SH) 3 domain to Akt proline-rich motifs. We also provide a novel model to depict how the interaction between PLC-gamma1 SH3 domain and Akt proline-rich motifs is dependent on EGF stimulation. In this model, phosphorylation of PLC-gamma1 Y783 by EGF causes the conformational change of PLC-gamma1 to allow the interaction of its SH3 domain with Akt proline-rich motifs. Furthermore, we showed that the interaction between PLC-gamma1 and Akt resulted in the phosphorylation of PLC-gamma1 S1248 by Akt. Finally, we showed that the interaction between PLC-gamma1 and Akt enhanced EGF-stimulated cell motility.
Wang
Yi
Y
Department of Cell Biology and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Wu
Jiliang
J
Wang
Zhixiang
Z
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002465:Cell Movement; D002522:Chlorocebus aethiops; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics
D004815:Epidermal Growth Factor; D011392:Proline; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma