Effect of serine and tyrosine phosphorylation on retroviral proteinase substrates

J. Tőzsér, P. Bagossi, Péter Boross, John M. Louis, Eva Majerova, Stephen Oroszlan, Terry D. Copeland

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Vimentin, a cellular substrate of HIV type 1 (HIV-1) proteinase, contains a protein kinase C (PKC) phosphorylation site at one of its cleavage sites. Peptides representing this site were synthesized in P2 Ser- phosphorylated and nonphosphorylated forms. While the nonphosphorylated peptide was a fairly good substrate of the enzyme, phosphorylation prevented hydrolysis. Phosphorylation of human recombinant vimentin by PKC prevented its processing within the head domain, where the phosphorylation occurred. Oligopeptides representing naturally occurring cleavage sites at the C- terminus of the Rous sarcoma virus integrase were assayed as substrates of the avian proteinase. Unlike the nonphosphorylated peptides, a Ser- phosphorylated peptide was not hydrolyzed by the enzyme at the Ser-Pro bond, suggesting the role of previously established phosphorylation in processing at this site. Ser-phosphorylated and Tyr-phosphorylated forms of model substrates were also tested as substrates of the HIV-1 and the avian retroviral proteinases. In contrast to the moderate effect of P4 Set phosphorylation, phosphorylation of P1 Tyr prevented substrate hydrolysis by HIV-1 proteinase. Substrate phosphorylation had substantially smaller effects on the hydrolysis by the avian retroviral proteinase. As the active retroviral proteinase as well as various protein kinases are incorporated into mature virions, substrate phosphorylation resulting in attenuation or prevention of proteolytic processing may have important consequences in the regulation of the retroviral life cycle as well as in virus-host cell interactions.

Original languageEnglish
Pages (from-to)423-429
Number of pages7
JournalEuropean Journal of Biochemistry
Volume265
Issue number1
DOIs
Publication statusPublished - Oct 1 1999

Fingerprint

Phosphorylation
Serine
Tyrosine
Peptide Hydrolases
Substrates
HIV Protease
HIV-1
Hydrolysis
Peptides
Vimentin
Viruses
Protein Kinase C
seryl-proline
Processing
Rous sarcoma virus
Integrases
Oligopeptides
Enzymes
Life Cycle Stages
Recombinant Proteins

Keywords

  • AMV proteinase
  • HIV proteinase
  • Phosphorylation
  • Retropepsins
  • Substrate specificity

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effect of serine and tyrosine phosphorylation on retroviral proteinase substrates. / Tőzsér, J.; Bagossi, P.; Boross, Péter; Louis, John M.; Majerova, Eva; Oroszlan, Stephen; Copeland, Terry D.

In: European Journal of Biochemistry, Vol. 265, No. 1, 01.10.1999, p. 423-429.

Research output: Contribution to journalArticle

Tőzsér, J. ; Bagossi, P. ; Boross, Péter ; Louis, John M. ; Majerova, Eva ; Oroszlan, Stephen ; Copeland, Terry D. / Effect of serine and tyrosine phosphorylation on retroviral proteinase substrates. In: European Journal of Biochemistry. 1999 ; Vol. 265, No. 1. pp. 423-429.
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