NF2 binds PAK1

Stable Identifier
R-HSA-5669158
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
NF2 binds PAK1
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

NF2 (Merlin) is a product of the tumor suppressor gene neurofibromatosis type 2 (NF2). NF2 binds to the PBD of PAK1 and prevents its activation (Kissil et al. 2003). In primary schwannoma tumor samples derived from patients with germline mutations in the NF2 gene, PAK1 activity is highly elevated (Yi et al. 2008) and essential for the malignant growth of NF2-deficient cells (Hirokawa et al. 2004). In complex with ERBIN (ERBB2IP), NF2 may also be involved in the inhibition of PAK2 activation (Wilkes et al. 2009).


The localization and function of NF2 may be modulated by PAK2-mediated phosphorylation and subsequent sumoylation (Rong et al. 2004, Qi et al. 2014).

Literature References
PubMed ID Title Journal Year
24166499 Merlin sumoylation is required for its tumor suppressor activity

Qi, Q, Liu, X, Brat, DJ, Ye, K

Oncogene 2014
15378014 Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression

Rong, R, Surace, EI, Haipek, CA, Gutmann, DH, Ye, K

Oncogene 2004
19289088 Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta

Wilkes, MC, Repellin, CE, Hong, M, Bracamonte, M, Penheiter, SG, Borg, JP, Leof, EB

Dev. Cell 2009
18829550 Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2

Yi, C, Wilker, EW, Yaffe, MB, Stemmer-Rachamimov, A, Kissil, JL

Cancer Res. 2008
15000491 A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor

Hirokawa, Y, Tikoo, A, Huynh, J, Utermark, T, Hanemann, CO, Giovannini, M, Xiao, GH, Testa, JR, Wood, J, Maruta, H

Cancer J 2004
14580336 Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1

Kissil, JL, Wilker, EW, Johnson, KC, Eckman, MS, Yaffe, MB, Jacks, T

Mol. Cell 2003
Participants
Input
Output
Participant Of
hasEvent
Orthologous Events
NF2 binds PAK1 (Bos taurus)
NF2 binds PAK1 (Caenorhabditis elegans)
NF2 binds PAK1 (Canis familiaris)
NF2 binds PAK1 (Danio rerio)
NF2 binds PAK1 (Drosophila melanogaster)
NF2 binds PAK1 (Gallus gallus)
NF2 binds PAK1 (Mus musculus)
NF2 binds PAK1 (Rattus norvegicus)
NF2 binds PAK1 (Sus scrofa)
NF2 binds PAK1 (Xenopus tropicalis)
Authored
Orlic-Milacic, M  (2015-02-02)
Rivero Crespo, F  (2014-12-26)
Created
Orlic-Milacic, M  (2015-01-30)