Phosphorylation is the switch that turns PEA-15 from tumor suppressor to tumor promoter.
Abnormal ERK signaling is implicated in many human diseases including cancer. This signaling cascade is a good target for the therapy of certain malignancies because of its important role in regulating cell proliferation and survival. The small phosphoprotein PEA-15 is a potent regulator of the ERK signaling cascade, and, by acting on this pathway, has been described to have both tumor-suppressor and tumor-promoter functions. However, the exact mechanism by which PEA-15 drives the outcome one way or the other remains unclear. We propose that the cellular environment is crucial in determining PEA-15 protein function by affecting the protein's phosphorylation state. We hypothesize that only unphosphorylated PEA-15 can act as a tumor-suppressor and that phosphorylation alters the interaction with binding partners to promote tumor development. In order to use PEA-15 as a prognostic marker or therapeutic target it is therefore important to evaluate its phosphorylation status.
Cancer Biology Program, University of Hawai'i Cancer Center, University of Hawai'i at Manoa, Honolulu, HI, USA.
Florian
F
Sulzmaier
John
J
Opoku-Ansah
Joe W
JW
Ramos
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding
D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases