| PROLINE-RICH (PXXP) MOTIFS IN HIV-1 NEF BIND TO SH3 DOMAINS OF A SUBSET OF SRC KINASES AND ARE REQUIRED FOR THE ENHANCED GROWTH OF NEF(+) VIRUSES BUT NOT FOR DOWN-REGULATION OF CD4 |
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| Author(s): SAKSELA K, CHENG GH, BALTIMORE D |
| Source: EMBO JOURNAL Volume: 14 Issue: 3 Pages: 484-491 Published: FEB 1 1995 |
| Times Cited: 380 References: 42 |
| Abstract: Human immunodeficiency virus (HIV) and simian immunodeficiency virus Nef proteins contain a conserved motif with the minimal consensus (PxxP) site for Src homology region 3 (SH3)-mediated protein-protein interactions. Nef PxxP motifs show specific binding to biotinylated SH3 domains of Hck and Lyn, but not to those of other tested Src family kinases or less related proteins. A unique cooperative role of a distant proline is also observed. Endogenous Hck of monocytic U937 cells can be specifically precipitated by matrix-bound HIV-1 Nef, but not by mutant protein lacking PxxP. Intact Nef PxxP motifs are dispensable for Nef-induced CD4 down-regulation, but are required for the higher in vitro replicative potential of Nef(+) viruses. Thus, CD4 down-regulation and promotion of viral growth are two distinct functions of Nef, and the latter is mediated via SH3 binding. |
| Document Type: Article |
| Language: English |
| Reprint Address: SAKSELA, K (reprint author), ROCKEFELLER UNIV, 1230 YORK AVE, NEW YORK, NY 10021 USA |
Addresses:
1. MIT, CAMBRIDGE, MA 02139 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: QF718 |
| ISSN: 0261-4189 |