The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the 'open' conformation and suppresses cell growth and motility

David H. Gutmann, Carrie A. Haipek, Stephen P. Burke, Chun Xiao Sun, Daniel R. Scoles, Stefan M. Pulst

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)825-834
Number of pages10
JournalHuman molecular genetics
Volume10
Issue number8
StatePublished - Apr 1 2001

Fingerprint Dive into the research topics of 'The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the 'open' conformation and suppresses cell growth and motility'. Together they form a unique fingerprint.

  • Cite this