Over-expression of GM1 enhances cell proliferation with epidermal growth factor without affecting the receptor localization in the microdomain in PC12 cells.
Sialic acid-containing glycosphingolipids, gangliosides, are expressed at high levels in the nerve tissues and various tumor cells. Although a number of studies on the roles of gangliosides in the regulation of cell proliferation have been performed, the mechanisms for the regulation are not well understood. We established PC12 transfectant cells over-expressing GM1 using cloned beta1,3-galactosyltransferase (EC: 2.4.1.62) cDNA, and analyzed their growth and growth signals with epidermal growth factor (EGF). Over-expression of GM1 enhanced the cell proliferation with EGF under low serum culture conditions. The phosphorylation levels of EGF receptor and downstream MAP kinases after EGF stimulation were sustained even after 60 min in the transfectant cells. In contrast with Swiss3T3 cells, in which we previously reported growth suppression with GM1 over-expression due to a dramatic change in the intracellular localization of PDGF receptor, PC12 transfectant cells with beta1,3-galactosyltransferase cDNA showed no clear changes in the intracellular localization of EGF receptor in the microdomain/raft fractionation experiments compared with the vector control cells. These results suggested that the effects of GM1 expression on the nature of microdomains and growth signals depend on the cell types and receptors analyzed.
Nishio
Masashi
M
Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
Tajima
Orie
O
Furukawa
Keiko
K
Urano
Takeshi
T
Furukawa
Koichi
K
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000096:biosynthesis* / Q000235:genetics; D005700:Galactosyltransferases / Q000235:genetics / Q000502:physiology; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D014162:Transfection
D011518:Proto-Oncogene Proteins; D005677:G(M1) Ganglioside; D004815:Epidermal Growth Factor; C108454:GD2 beta1,3-galactosyltransferase; D005700:Galactosyltransferases; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3