Differential Ca2+ Signaling Induced by Activation of the Epidermal Growth Factor and Nerve Growth Factor Receptors
| Autor: | Stefan Mayr, Paul Dietl, Axel Obermeier, Hans Grunicke, Inge Tinhofer, Franz Hochholdinger, Karl Maly |
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| Rok vydání: | 1996 |
| Předmět: |
chemistry.chemical_element
Receptors Nerve Growth Factor Calcium Phospholipase Biology Biochemistry Proto-Oncogene Proteins p21(ras) Mice Cytosol Epidermal growth factor Extracellular Animals Binding site Receptor Molecular Biology Phospholipase C gamma 3T3 Cells Cell Biology Molecular biology ErbB Receptors Isoenzymes chemistry Type C Phospholipases Trk receptor Signal Transduction Binding domain |
| Zdroj: | Journal of Biological Chemistry. 271:30505-30509 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.48.30505 |
| Popis: | Stimulation by epidermal growth factor (EGF) of NIH3T3 cells overexpressing the EGF receptor (EGFR) results in a release of Ca2+ from internal stores. Ca2+ release is followed by an influx of extracellular calcium which can be recorded by the influx of the calcium surrogate Mn2+. Both Ca2+ release and Mn2+/Ca2+ influx are inhibited by expression of the dominant negative Asn17-Ras mutant and abrogated by microinjected neutralizing anti-Ras antibody Y13-259, whereas microinjection of the anti-Ras antibody Y13-238 which does not interact with the effector binding domain of Ras is without any effect on the EGF-induced Ca2+ transient. Neither Asn17-Ha-Ras nor the Y13-259 antibody interferes with the thapsigargin-induced Mn2+/Ca2+ influx. The nerve growth factor receptor (Trk)-mediated Ca2+ transient was found to be unaffected by the dominant negative Ras mutant or microinjected neutralizing anti-Ras antibodies. Substitution of the phospholipase Cgamma1 (PLCgamma1) binding site of the EGFR by the PLCgamma binding domain of Trk renders the EGFR-induced Ca2+ influx insensitive to the expression of Asn17-Ha-Ras, whereas the Ca2+ signal induced by Trk carrying the PLC binding site of EGFR is Ras-dependent and abrogated by the dominant negative Ras mutant. It is concluded that the Ca2+ transient induced by the activated EGFR, not, however, the Ca2+ transient elicited by the activated NGFR/Trk, is a Ras-mediated phenomenon and that the role of Ras in regulating EGFR-induced Ca2+ influx depends on the structure of the PLCgamma binding domain. |
| Databáze: | OpenAIRE |
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