Reactome | NF2 binds PAK1

NF2 binds PAK1

Stable Identifier

R-HSA-5669158

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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
15378014	Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression Gutmann, DH, Rong, R, Ye, K, Haipek, CA, Surace, EI	Oncogene	2004
24166499	Merlin sumoylation is required for its tumor suppressor activity Qi, Q, Liu, X, Brat, DJ, Ye, K	Oncogene	2014
19289088	Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta Leof, EB, Wilkes, MC, Bracamonte, M, Borg, JP, Repellin, CE, Penheiter, SG, Hong, M	Dev. Cell	2009
18829550	Validation of the p21-activated kinases as targets for inhibition in neurofibromatosis type 2 Yi, C, Wilker, EW, Kissil, JL, Stemmer-Rachamimov, A, Yaffe, MB	Cancer Res.	2008
15000491	A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor Giovannini, M, Hirokawa, Y, Utermark, T, Hanemann, CO, Tikoo, A, Testa, JR, Maruta, H, Wood, J, Xiao, GH, Huynh, J	Cancer J	2004
14580336	Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1 Jacks, T, Wilker, EW, Eckman, MS, Kissil, JL, Yaffe, MB, Johnson, KC	Mol. Cell	2003