Protein phosphotyrosine in mouse brain: developmental changes and regulation by epidermal growth factor, type I insulin-like growth factor, and insulin.
Using antiphosphotyrosine antibodies, we have investigated protein phosphorylation in mouse brain during development in intact animals and in reaggregated cerebral cultures. Under basal conditions, in vivo and in vitro, the levels of two main phosphoproteins, of Mr 120,000 and 180,000 (pp180), increased with development, reaching a maximum in the early postnatal period and decreasing thereafter. In adult forebrain, pp180 was still highly phosphorylated, but it was not detected in cerebellum or in peripheral tissues. In reaggregated cortical cultures, epidermal growth factor (EGF), type I insulin-like growth factor (IGF-I), and insulin enhanced protein tyrosine phosphorylation of several proteins, which were specific for EGF or IGF-I/insulin. In highly enriched neuronal or astrocytic monolayer cultures, some proteins phosphorylated in basal conditions, or in response to EGF and IGF-I, were found in both types of culture, whereas others appeared cell type specific. In addition, in each cell type, some proteins were phosphorylated under the action of both growth factors. These results indicate that tyrosine protein phosphorylation is maximal in mouse brain during development and is regulated by growth factors in neurons as well as in astrocytes.
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York.
J A
JA
Girault
B
B
Chamak
G
G
Bertuzzi
H
H
Tixier
J K
JK
Wang
D T
DT
Pang
P
P
Greengard
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D002449:Cell Aggregation; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D007328:Insulin; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I