Sustained formation of focal adhesions with paxillin in morphological differentiation of PC12 cells.
Differentiation of PC12 cells triggered by nerve growth factor (NGF) is characterized by several well-defined events including induction of a set of neuron-specific genes, gain of membrane excitability, and morphological changes such as neurite outgrowth. Here we report that K252a, a protein kinase inhibitor, converts the proliferation signal of epidermal growth factor (EGF) into the morphological differentiation signal without inducing the sustained activation of ERK and the expression of neurofilament. Major effects of EGF/K252a, found also in the NGF-treated cells, are the sustained mobility shift of paxillin in SDS-PAGE and the promoted association of Crk-II with paxillin. These effects explain the prominent and robust development of peripheral focal adhesion assembly and stress fiber-like structures observed in the early stages of PC12 cell differentiation. These results suggest a model that cytoskeletal reorganization via focal adhesion assembly triggered by NGF provides a signal required for the morphological differentiation of PC12 cells.
Rhee
S
S
Department of Molecular Biology, Dankook University, Seoul, Korea.
Lee
K H
KH
Kim
D
D
Kwon
Y K
YK
Kang
M S
MS
Kwon
H
H
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002227:Carbazoles / Q000378:metabolism / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation; D016895:Culture Media, Serum-Free; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D026121:Indole Alkaloids; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D051419:Paxillin; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D002227:Carbazoles; D016895:Culture Media, Serum-Free; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020928:Mitogen-Activated Protein Kinases