Differential signalling pathways for EGF versus PDGF activation of Erk1/2 MAP kinase and cell proliferation in brown pre-adipocytes.
Stimulation by both adrenergic and non-adrenergic pathways can induce proliferation of brown pre-adipocytes. To understand the signalling pathways involved in non-adrenergic stimulation of cell proliferation, we examined Erk1/2 activation. In primary cultures of mouse brown pre-adipocytes, both EGF (epidermal growth factor) and PDGF (platelet-derived growth factor) induced Erk1/2 activation. EGF-stimulated Erk1/2 activation involved Src tyrosine kinases, but not PKC or PI3K, whereas in PDGF-induced Erk1/2 activation, PI3K, PKC (probably the atypical zeta isoform) and Src were involved sequentially. Both EGF and PDGF induced PI3K-dependent Akt activation that was not involved in Erk1/2 activation. By comparing effects of signalling inhibitors (wortmannin, SH-6, TPA, Gö6983, PP2, PD98059) on EGF- and PDGF-induced Erk1/2 activation and cell proliferation (3H-thymidine incorporation), we conclude that while the signal transduction pathways initiated by these growth factors are clearly markedly different, their effects on cell proliferation can be fully explained through their stimulation of Erk1/2 activation; thus Erk1/2 is a common, essential step for stimulation of proliferation in these cells.
Department of Physiology, The Wenner-Gren Institute, The Arrhenius laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Therese E
TE
Holmström
Charlotte L
CL
Mattsson
Johanna M
JM
Fälting
Jan
J
Nedergaard
D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology; D019061:src-Family Kinases / Q000378:metabolism
D005419:Flavonoids; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D019061:src-Family Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one