Lipase inactive mutant of PLC-gamma1 regulates NGF-induced neurite outgrowth via enzymatic activity and regulation of cell cycle regulatory proteins.
Src homology (SH) domains of phospholipase C-gamma1 (PLC-gamma1) impair NGF-mediated PC12 cells differentiation. However, whether the enzymatic activity is also implicated in this process remains elusive. Here, we report that the enzymatic activity of phospholipase C-gamma1 (PLC-gamma1) is at least partially involved to the blockage of neuronal differentiation via an abrogation of MAPK activation, as well as sustained Akt activation. By contrast, Overexpression of WT-PLC-gamma1 exhibited sustained NGF-induced MAPK activation, and triggered transient Akt activation resulting in profound inhibition of neurite outgrowth. However, lipase-inactive mutant (LIM) PLC-gamma1 cells fail to suppress neurite outgrowth, although it contains intact SH domains, specifically enhancing the expression of cyclin D1 and p21 proteins, which regulate the function of retinoblastoma Rb protein. These observations show that the lipase inactive mutant of PLC-gamma1 does not alter NGF-induced neuronal differentiation via enzymatic inability and the odulation of cell cycle regulatory proteins independent on SH3 domain.
Nguyen
Truong Le Xuan
Tle X
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Ahn
Jee-Yin
JY
D019943:Amino Acid Substitution; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016716:PC12 Cells; D051966:Phospholipase C gamma / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D020932:Nerve Growth Factor; D051966:Phospholipase C gamma