Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation.
Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.
Kratchmarova
Irina
I
Center for Experimental BioInformatics (CEBI), Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Blagoev
Blagoy
B
Haack-Sorensen
Mandana
M
Kassem
Moustapha
M
Mann
Matthias
M
D002454:Cell Differentiation; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D008648:Mesoderm / Q000166:cytology*; D020932:Nerve Growth Factor / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D040901:Proteomics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014443:Tyrosine / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D011506:Proteins; D014443:Tyrosine; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases