Enhancement of the mitogenic effect by artificial juxtacrine stimulation using immobilized EGF.
Mouse epidermal growth factor (EGF) was covalently conjugated with the water-soluble polymer, poly(acrylic acid) (EGF-PAA), or with the water-insoluble polymer, surface-hydrolyzed poly(methyl methacrylate) (EGF-PMMA). Immobilized EGF (EGF-PMMA) stimulated DNA synthesis in Chinese hamster ovary cells overexpressing EGF receptors in amounts that were 5 to 10% of those of free EGF required for comparable effects. In addition, the maximal mitogenic effect of EGF-PMMA was greater than that of unconjugated EGF or EGF-PAA. EGF, EGF-PAA, and EGF-PMMA induced the autophosphorylation of EGF receptors and the stimulation of mitogen-activated protein kinase. However, whereas the onset of these effects was delayed with EGF-PMMA, they persisted for much longer than those of EGF and EGF-PAA. Unlike EGF and EGF-PAA, EGF-PMMA was not associated with cells after their removal from culture and did not induce receptor internalization. Culturing cells with PMMA-immobilized EGF thus represents a model system for studying "juxtacrine" stimulation of cells by membrane-bound growth factors.
Ito
Y
Y
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku. h51535@sakura.kudpc.kyoto-u.ac.jp
Li
J S
JS
Takahashi
T
T
Imanishi
Y
Y
Okabayashi
Y
Y
Kido
Y
Y
Kasuga
M
M
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D008768:Methylmethacrylates / Q000737:chemistry; D051379:Mice; D010766:Phosphorylation
D000180:Acrylic Resins; D008768:Methylmethacrylates; C006903:carbopol 940; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases