PMID- 10544125
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20151119
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 264
IP  - 1
DP  - 1999 Nov 10
TI  - The conserved core of human immunodeficiency virus type 1 Nef is essential for
      association with Lck and for enhanced viral replication in T-lymphocytes.
PG  - 5-15
AB  - The Nef protein of the primate lentiviruses, including human immunodeficiency
      virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), is a myristylated
      protein associated with increased viral replication and enhanced pathogenicity.
      Both the potentiation of T-lymphocyte activation and the enhanced
      serine-phosphorylation of HIV-1 capsid by Nef correlate with increased viral
      replication. We report the functional interactions of the Nef proteins with Src
      kinases. The Nef proteins from HIV-1 and SIV bind to Lck as well as Hck, Lyn, and
      Fyn. The SH3 and SH2 domains of Lck are sufficient for coprecipitation with
      non-tyrosine-phosphorylated Nef proteins. The conserved core region of HIV-1 Nef 
      is essential for the interaction with Lck and is also important for enhanced
      HIV-1 replication in T-lymphocytes. In addition, we show that SIV and HIV-1 Nef
      proteins are differentially tyrosine-phosphorylated. The kinase-active Lck
      tyrosine-phosphorylates SIVmac239 Nef but does not phosphorylate HIV-1 Nef. These
      data suggest that the association of Nef and Lck is central to the enhanced viral
      replication of HIV-1 and SIV in T-lymphocytes.
CI  - Copyright 1999 Academic Press.
FAU - Cheng, H
AU  - Cheng H
AD  - Department of Microbiology and Pediatrics, New York University School of
      Medicine, New York, New York 10016, USA.
FAU - Hoxie, J P
AU  - Hoxie JP
FAU - Parks, W P
AU  - Parks WP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Gene Products, nef)
RN  - 0 (Recombinant Proteins)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
SB  - X
MH  - Base Sequence
MH  - Cell Line
MH  - Conserved Sequence
MH  - Gene Products, nef/genetics/metabolism
MH  - *Genes, nef
MH  - HIV-1/genetics/*physiology
MH  - Humans
MH  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Recombinant Proteins/metabolism
MH  - Sequence Deletion
MH  - Simian Immunodeficiency Virus/genetics/physiology
MH  - T-Lymphocytes/*physiology/*virology
MH  - Transfection
MH  - Virus Replication/*genetics
MH  - nef Gene Products, Human Immunodeficiency Virus
MH  - src-Family Kinases/metabolism
EDAT- 1999/11/02 00:00
MHDA- 1999/11/02 00:01
CRDT- 1999/11/02 00:00
PHST- 1999/11/02 00:00 [pubmed]
PHST- 1999/11/02 00:01 [medline]
PHST- 1999/11/02 00:00 [entrez]
AID - 10.1006/viro.1999.9937 [doi]
AID - S0042682299999373 [pii]
PST - ppublish
SO  - Virology. 1999 Nov 10;264(1):5-15. doi: 10.1006/viro.1999.9937.