title: MS-430, a synthetic pyrimidine derivative, influences the intracellular signal transduction pathway leading to neuronal differentiation of PC12h cells.
abstract: Although NGF (nerve growth factor) induces neuronal differentiation of PC12 cells, EGF (epidermal growth factor) acts as a mitogen for these cells. We have studied the effects of a synthetic pyrimidine derivative, MS-430, on the NGF and EGF actions on PC12h cells. We found that MS-430 accelerated NGF-induced neurite extension of PC12h cells and that, in the presence of MS-430, PC12h cells extended neurites in response to EGF. Next, we investigated the tyrosine phosphorylation of NGF receptor TrkA and the EGF receptor (EGFR) as well as mitogen-activated protein kinase (MAPK), which is a key protein in the intracellular signal transduction pathway. It was found that MS-430 prolonged the EGF-induced phosphorylation of EGFR and MAPK compared to that without MS-430. MS-430 also prolonged the NGF-induced phosphorylation of MAPK, but the phosphorylation of TrkA induced by NGF was not affected by MS-430. These results suggest that MS-430 influences the intracellular signal transduction pathway which causes the neuronal differentiation of PC12h cells.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565, Japan. ikeuchi@protein.osaka-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: A
authors.initials: A
authors.lastname: Nakatani
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Itokazu
authors.forename: A
authors.initials: A
authors.lastname: Awaya
authors.forename: H
authors.initials: H
authors.lastname: Hatanaka
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
chemical_list: C093088:MS 430; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D017475:Receptors, Nerve Growth Factor; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000110:Acetylcholinesterase