The urokinase plasminogen activator receptor (UPAR) is preferentially induced by nerve growth factor in PC12 pheochromocytoma cells and is required for NGF-driven differentiation.
Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation. A "second generation" representational difference analysis procedure now identifies the urokinase plasminogen activator receptor (UPAR) as a gene that is much more extensively induced by NGF than by EGF in PC12 cells. Both an antisense oligonucleotide for the UPAR mRNA and an antibody directed against UPAR protein block NGF-induced morphological and biochemical differentiation of PC12 cells; NGF-induced UPAR expression is required for subsequent NGF-driven differentiation.
Farias-Eisner
R
R
Department of Obstetrics and Gynecology, University of California, Los Angeles, Center for the Health Sciences, Los Angeles, California, USA.
Vician
L
L
Silver
A
A
Reddy
S
S
Rabbani
S A
SA
Herschman
H R
HR
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D015152:Blotting, Northern; D002454:Cell Differentiation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000906:Antibodies; D016375:Antisense Elements (Genetics); C524900:Plaur protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D014568:Urokinase-Type Plasminogen Activator