Adenosine A(2A) receptor mRNA regulation by nerve growth factor is TrkA- , Src-, and Ras-dependent via extracellular regulated kinase and stress- activated protein kinase/c-Jun NH2-terminal kinase
Journal of Biological Chemistry
We have shown previously that nerve growth factor (NGF) down-regulates adenosine A(2A) receptor (A(2A)AR) mRNA in PC12 cells. To define cellular mechanisms that modulate A(2A)AR expression, A(2A)AR mRNA and protein levels were examined in three PC12 sublines: i) PC12nnr5 cells, which lack the high affinity NGF receptor TrkA, ii) srcDN2 cells, which overexpress kinase- defective Src, and iii) 17.26 cells, which overexpress a dominant-inhibitory Ras. In the absence of functional TrkA, Src, or Ras, NGF-induced down- regulation of A(2A)AR mRNA and protein was significantly impaired. However, regulation of A(2A)AR expression was reconstituted in PC12nnr5 cells stably transfected with TrkA. Whereas NGF stimulated the mitogen-activated protein kinases p38, extracellular regulated kinase 1 and 2 (ERK1/ERK2), and stress- activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) in PC12 cells, these kinases were activated only partially or not at all in srcDN2 and 17.26 cells. Inhibiting ERK1/ERK2 with PD98059 or inhibiting SAPK/JNK by transfecting cells with a dominant-negative SAPKβ/JNK3 mutant partially blocked NGF-induced down-regulation of A(2A)AR expression in PC12 cells. In contrast, inhibiting p38 with SB203580 had no effect on the regulation of A(2A)AR mRNA and protein levels. Treating SAPKβ/JNK3 mutant-transfected PC12 cells with PD98059 completely abolished the NGF-induced decrease in A(2A)AR mRNA and protein levels. These results reveal a role for ERKI/ERK2 and SAPK/JNK in regulating A(2A)AR expression.
Malek, R., Nie, Z., Ramkumar, V., & Lee, N. (1999). Adenosine A(2A) receptor mRNA regulation by nerve growth factor is TrkA- , Src-, and Ras-dependent via extracellular regulated kinase and stress- activated protein kinase/c-Jun NH2-terminal kinase. Journal of Biological Chemistry, 274 (50). http://dx.doi.org/10.1074/jbc.274.50.35499