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Journal of Virology, July 1999, p. 6152-6158, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

Alison L. Greenway,1 Hélène Dutartre,2 Kelly Allen,1 Dale A. McPhee,1 Daniel Olive,2 and Yves Collette2,*

U119 INSERM, Université de Méditerranée, 13009 Marseille, France,2 and AIDS Cellular Biology Unit, Macfarlane Burnet Center for Medical Research, Fairfield, Victoria 3078, Australia1

Received 16 September 1998/Accepted 8 March 1999

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases.

* Corresponding author. Mailing address: U119 INSERM, Université de Méditerannée, 27, Boulevard Leï Roure, 13009 Marseille, France. Phone: (33) 491 75 84 13. Fax: (33) 491 26 03 64. E-mail: collette{at}marseille.inserm.fr.

Journal of Virology, July 1999, p. 6152-6158, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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