p21-activated kinase links Rac/Cdc42 signaling to merlin.

p21-activated kinase links Rac/Cdc42 signaling to merlin. Research Abstract Details 

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p21-activated kinase links Rac/Cdc42 signaling to merlin. Abstract Text:

Guang-Hui Xiao,Alexander Beeser,Jonathan Chernoff,Joseph R Testa,

The neurofibromatosis type 2 tumor suppressor gene, NF2, is mutated in the germ line of NF2 patients and predisposes affected individuals to intracranial and spinal tumors. Moreover, somatic mutations of NF2 can occur in the sporadic counterparts of these neurological tumor types as well as in certain neoplasms of non-neuroectodermal origin, such as malignant mesothelioma and melanoma. NF2 encodes a 595-amino acid protein, merlin, which exhibits significant homology to the ezrin-radixin-moesin family of proteins. However, the mechanism by which merlin exerts its tumor suppressor activity is not well understood. In this investigation, we show that merlin is phosphorylated in response to expression of activated Rac and activated Cdc42 in mammalian cells. Furthermore, we demonstrate that merlin phosphorylation is mediated by p21-activated kinase (Pak), a common downstream target of both Rac and Cdc42. Both in vivo and in vitro kinase assays demonstrated that Pak can directly phosphorylate merlin at serine 518, a site that affects merlin activity and localization. These biochemical investigations provide insights into the regulation of merlin function and establish a framework for elucidating tumorigenic mechanisms involved in neoplasms associated with merlin inactivation.

p21-activated kinase links Rac/Cdc42 signaling to merlin. Publishing Authors By Initials

GH Xiao,A Beeser,J Chernoff,JR Testa,

For similar enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: rac gtp-binding proteins research abstracts see: enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: rac gtp-binding proteins research

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p21-activated kinase links Rac/Cdc42 signaling to merlin. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 277

Page Numbers: 883-6

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 21

MONTH: 11

YEAR: 2001

p21-activated kinase links Rac/Cdc42 signaling to merlin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

p21-activated kinase links Rac/Cdc42 signaling to merlin. Keywords Mesh Terms:

KEYWORDS: rac GTP-Binding Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: p21-activated kinase links Rac/Cdc42 signaling to merlin. Information

Substance Name: rac GTP-Binding Proteins

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for p21-activated kinase links Rac/Cdc42 signaling to merlin.

AFFILIATION: Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM54168

ACRONYM: GM

MEDLINETA: J Biol Chem

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