Human Molecular Genetics, 2001, Vol. 10, No. 8 825-834
© 2001 Oxford University Press
The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the ‘open’ conformation and suppresses cell growth and motility
1Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St Louis, MO 63110, USA and 2Division of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
The neurofibromatosis 2 tumor suppressor protein, merlin or schwannomin, functions as a negative growth regulator; however, its mechanism of action is not known. In an effort to determine how merlin regulates cell growth, we analyzed a recently identified novel merlin interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS). We demonstrate that regulated overexpression of HRS in rat schwannoma cells results in similar effects as overexpression of merlin, including growth inhibition, decreased motility and abnormalities in cell spreading. Previously, we showed that merlin forms an intramolecular association between the N- and C-termini and exists in ‘open’ and ‘closed’ conformations. Merlin interacts with HRS in the unfolded, or open, conformation. This HRS binding domain maps to merlin residues 453–557. Overexpression of C-terminal merlin has no effect on HRS function, arguing that merlin binding to HRS does not negatively regulate HRS growth suppressor activity. These results suggest the possibility that merlin and HRS may regulate cell growth in schwannoma cells through interacting pathways.
+ To whom correspondence should be addressed. Tel: +1 314 362 7149; Fax: +1 314 362 2388; Email: gutmannd@neuro.wustl.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Lallemand, A. L. Saint-Amaux, and M. Giovannini Tumor-suppression functions of merlin are independent of its role as an organizer of the actin cytoskeleton in Schwann cells J. Cell Sci., November 15, 2009; 122(22): 4141 - 4149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yi, J. H. McCarty, S. A. Troutman, M. S. Eckman, R. T. Bronson, and J. L. Kissil Loss of the Putative Tumor Suppressor Band 4.1B/Dal1 Gene Is Dispensable for Normal Development and Does Not Predispose to Cancer Mol. Cell. Biol., November 15, 2005; 25(22): 10052 - 10059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Walter-Yohrling, X. Cao, M. Callahan, W. Weber, S. Morgenbesser, S. L. Madden, C. Wang, and B. A. Teicher Identification of Genes Expressed in Malignant Cells That Promote Invasion Cancer Res., December 15, 2003; 63(24): 8939 - 8947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-X. Sun, C. Haipek, D. R. Scoles, S. M. Pulst, M. Giovannini, M. Komada, and D. H. Gutmann Functional analysis of the relationship between the neurofibromatosis 2 tumor suppressor and its binding partner, hepatocyte growth factor-regulated tyrosine kinase substrate Hum. Mol. Genet., December 1, 2002; 11(25): 3167 - 3178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Scoles, V. D. Nguyen, Y. Qin, C.-X. Sun, H. Morrison, D. H. Gutmann, and S.-M. Pulst Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling Hum. Mol. Genet., December 1, 2002; 11(25): 3179 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-X. Sun, V. A. Robb, and D. H. Gutmann Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation J. Cell Sci., November 1, 2002; 115(21): 3991 - 4000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kressel and B. Schmucker Nucleocytoplasmic transfer of the NF2 tumor suppressor protein merlin is regulated by exon 2 and a CRM1-dependent nuclear export signal in exon 15 Hum. Mol. Genet., September 15, 2002; 11(19): 2269 - 2278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Gutmann, A. C. Hirbe, and C. A. Haipek Functional analysis of neurofibromatosis 2 (NF2) missense mutations Hum. Mol. Genet., July 1, 2001; 10(14): 1519 - 1529. [Abstract] [Full Text] [PDF]
|
|