Human Molecular Genetics, 2003, Vol. 12, No. 11 1211-1221
DOI: 10.1093/hmg/ddg146
© 2003 Oxford University Press
Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells
Department of Neurology, Zentrum für klinische Forschung, University of Ulm, Helmholtzstr 8/1, 89081 Ulm, Germany
Received March 3, 2003; Revised March 27, 2003; Accepted April 4, 2003
Schwann cells lacking the tumor-suppressor-protein merlin tend in man to build benign tumors (schwannoma). We observed that characteristic features of these cells which are relevant to tumorigenicity resemble those described in cells with high Rac activity. Moreover this small GTPase also phosphorylates merlin via PAK activation. We hypothesized that merlin deficiency might cause an activation of Rac and its dependent signaling pathways, in particular the pro-tumorigenic JNK pathway. We show an enhanced activation of Rac1 in primary human schwannoma cells, find both Rac and its effector PAK at the membrane where they colocalize, and describe increased levels of phosphorylated JNK in the nucleus of these cells. Further we describe regulation at post-transcriptional level with upregulated protein, but not mRNA levels for Rac1, and JNK1/2. We conclude that merlin regulates Rac activation, and suggest that this is important for human schwannoma cell dedifferentiation.
* To whom correspondence should be addressed. Tel: +49 73150033640; Fax: +49 73150033609; Email: oliver.hanemann{at}medizin.uni-ulm.de
Present address: Institute of Physiological Biochemistry, Medical School Hannover, 30625 Hannover, Germany.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Ammoun, C. Flaiz, N. Ristic, J. Schuldt, and C. O. Hanemann Dissecting and Targeting the Growth Factor-Dependent and Growth Factor-Independent Extracellular Signal-Regulated Kinase Pathway in Human Schwannoma Cancer Res., July 1, 2008; 68(13): 5236 - 5245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. O. Hanemann Magic but treatable? Tumours due to loss of Merlin Brain, March 1, 2008; 131(3): 606 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nodari, D. Zambroni, A. Quattrini, F. A. Court, A. D'Urso, A. Recchia, V. L.J. Tybulewicz, L. Wrabetz, and M. L. Feltri {beta}1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination J. Cell Biol., July 30, 2007; 177(6): 1063 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakai, Y. Zheng, M. MacCollin, and N. Ratner Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells. J. Neurosci., March 29, 2006; 26(13): 3390 - 3395. [Abstract] [Full Text] [PDF]
|
|