This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerber, M. A. Articles by Gutmann, D. H. Search for Related Content PubMed PubMed Citation Articles by Gerber, M. A. Articles by Gutmann, D. H.

Protein 4.1B/Differentially Expressed in Adenocarcinoma of the Lung-1 Functions as a Growth Suppressor in Meningioma Cells by Activating Rac1-Dependent c-Jun-NH₂-kinase Signaling

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri

Requests for reprints: David H. Gutmann, Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110. Phone: 314-362-7379; Fax: 314-362-2388; E-mail: gutmannd{at}neuro.wustl.edu.

Meningiomas are the second most common brain tumor in adults, yet comparatively little is presently known about the dysregulated growth control pathways involved in their formation and progression. One of the most frequently observed genetic changes in benign meningioma involves loss of protein 4.1B expression. Previous studies from our laboratory have shown that protein 4.1B growth suppression in meningioma is associated with the activation of the c-Jun-NH₂-kinase (JNK) pathway and requires localization of a small unique region (U2 domain) of protein 4.1B to the plasma membrane. To define the relationship between protein 4.1B expression and JNK activation, as well as to determine the mechanism of JNK activation by protein 4.1B, we used a combination of genetic and pharmacologic approaches. In this report, we show that protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 (DAL-1) expression in meningioma cells in vitro results in JNK activation, which requires the sequential activation of Src, Rac1, and JNK. In addition, inhibition of Rac1 or JNK activation abrogates protein 4.1B/DAL-1 growth suppression and cyclin A regulation. Last, protein 4.1B/DAL-1 regulation of this critical growth control pathway in meningioma cells requires the presence of the U2 domain. Collectively, these observations provide the first mechanistic insights into the function of protein 4.1B as a growth regulator in meningioma cells. (Cancer Res 2006; 66(10): 5295-303)

This article has been cited by other articles:

				S. S. Houshmandi, R. J. Emnett, M. Giovannini, and D. H. Gutmann The Neurofibromatosis 2 Protein, Merlin, Regulates Glial Cell Growth in an ErbB2- and Src-Dependent Manner Mol. Cell. Biol., March 15, 2009; 29(6): 1472 - 1486. [Abstract] [Full Text] [PDF]

				S. Y. Wong, H. Haack, J. L. Kissil, M. Barry, R. T. Bronson, S. S. Shen, C. A. Whittaker, D. Crowley, and R. O. Hynes Protein 4.1B suppresses prostate cancer progression and metastasis PNAS, July 31, 2007; 104(31): 12784 - 12789. [Abstract] [Full Text] [PDF]