CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1.

CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Research Abstract Details 

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CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Abstract Text:

X Lu,X Wu,A Plemenitas,H Yu,E T Sawai,A Abo,B M Peterlin,

BACKGROUND: The negative factor (Nef) of human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV) is required for high levels of viremia and progression to AIDS. Additionally, Nef leads to cellular activation, increased viral infectivity and decreased expression of CD4 on the cell surface. Previously, we and others demonstrated that Nef associates with a cellular serine kinase (NAK) activity. Recently, it was demonstrated that NAK bears structural and functional similarity to p21-activated kinases (PAKs). RESULTS: In this study, we demonstrate that Nef not only binds to but also activates NAK via the small GTPases CDC42 and Rac1. First, the dominant-negative PAK (PAKR), via its GTPase-binding domain, and dominant-negative GTPases (CDC42Hs-N17 and Rac1-N17) block the ability of Nef to associate with and activate NAK. Second, constitutively active small GTPases (CDC42Hs-V12 and Rac1-V12) potentiate the effects of Nef. Third, interactions between Nef and NAK result in several cellular effector functions, such as activation of the serum-response pathway. And finally, PAKR, CDC42Hs-N17 and Rac1-N17 decrease levels of HIV-1 production to those of virus from which the nef gene is deleted. CONCLUSIONS: By activating NAK via small GTPases and their downstream effectors, Nef interacts with regulatory pathways required for cell growth, cytoskeletal rearrangement and endocytosis. Thus, NAK could participate in the budding of new virions, the modification of viral proteins and the increased endocytosis of surface molecules such as CD4. Moreover, blocking the activity of these GTPases could lead to new therapeutic interventions against AIDS.

CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Publishing Authors By Initials

X Lu,X Wu,A Plemenitas,H Yu,ET Sawai,A Abo,BM Peterlin,

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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CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Journal Published:

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

Journal: Current biology : CB

VOLUME: 6

Page Numbers: 1677-84

Journal Abbreviation: Curr. Biol.

ISSN: 0960-9822

DAY: 1

MONTH: Dec

YEAR: 1996

CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9107782

CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Keywords Mesh Terms:

KEYWORDS: rac GTP-Binding Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1. Information

Substance Name: rac GTP-Binding Proteins

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1.

AFFILIATION: Howard Hughes Medical Institute, University of California at San Francisco, California, USA.

Country: ENGLAND

AGENCY: United States NIAID

GRANT: 1RO1AI38532-01

ACRONYM: AI

MEDLINETA: Curr Biol

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