TY - JOUR
T1 - Activation of Ras is necessary and sufficient for upregulation of vanilloid receptor type 1 in sensory neurons by neurotrophic factors
AU - Bron, Romke
AU - Klesse, Laura J.
AU - Shah, Kirti
AU - Parada, Luis F.
AU - Winter, Janet
N1 - Funding Information:
We are grateful to Dr E. Caron and Professor A. Hall for their gift of the Myc-tagged Ras and Rap constructs. L.F.P. and L.J.K. were supported by NINDS.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - We have analyzed signaling pathways involved in neurotrophic factor (NTF)-induced upregulation of nociceptive properties, specifically vanilloid receptor type 1 (VR1), by adult rat dorsal root ganglion neurons. Upregulation of VR1 by nerve growth factor and glial cell line-derived neurotrophic factor is partially blocked by a MEK inhibitor. Dominant negative Ras, but not Rap, blocks NTF-induced ERK activation and VR1 upregulation. Activated Ras mimics NTF-mediated induction of VR1 in dorsal root ganglion neurons. An inhibitor of phosphatidylinositol 3-kinase, LY294002, also inhibited NTF-induced VR1 upregulation. However, this may at least in part be due to a block of NTF-induced ERK activation. Constitutive simultaneous stimulation of both ERK and phosphatidylinositol 3-kinase is not sufficient for VR1 upregulation. Together, the data suggest that VR1 expression by dorsal root ganglion neurons is regulated by common Ras-dependent pathways.
AB - We have analyzed signaling pathways involved in neurotrophic factor (NTF)-induced upregulation of nociceptive properties, specifically vanilloid receptor type 1 (VR1), by adult rat dorsal root ganglion neurons. Upregulation of VR1 by nerve growth factor and glial cell line-derived neurotrophic factor is partially blocked by a MEK inhibitor. Dominant negative Ras, but not Rap, blocks NTF-induced ERK activation and VR1 upregulation. Activated Ras mimics NTF-mediated induction of VR1 in dorsal root ganglion neurons. An inhibitor of phosphatidylinositol 3-kinase, LY294002, also inhibited NTF-induced VR1 upregulation. However, this may at least in part be due to a block of NTF-induced ERK activation. Constitutive simultaneous stimulation of both ERK and phosphatidylinositol 3-kinase is not sufficient for VR1 upregulation. Together, the data suggest that VR1 expression by dorsal root ganglion neurons is regulated by common Ras-dependent pathways.
UR - http://www.scopus.com/inward/record.url?scp=0037282830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037282830&partnerID=8YFLogxK
U2 - 10.1016/S1044-7431(02)00022-2
DO - 10.1016/S1044-7431(02)00022-2
M3 - Article
C2 - 12595244
AN - SCOPUS:0037282830
SN - 1044-7431
VL - 22
SP - 118
EP - 132
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 1
ER -