Document 0542
 DOCN  M9590542
 TI    An octapeptide analogue of HIV gp120 modulates protein tyrosine kinase
       activity in activated peripheral blood T lymphocytes.
 DT    9509
 AU    Phipps DJ; Reed-Doob P; MacFadden DK; Piovesan JP; Mills GB; Branch DR;
       Toronto Hospital, Ontario, Canada.
 SO    Clin Exp Immunol. 1995 Jun;100(3):412-8. Unique Identifier : AIDSLINE
       MED/95292387
 AB    Following infection with HIV, patients exhibit lymphocyte dysfunction
       before the loss of CD4+ T cells. The major HIV surface glycoprotein,
       gp120, can modulate lymphocyte function in vitro; however, the mechanism
       by which gp120 affects T lymphocyte signal transduction is
       controversial. We have used Peptide T, a synthetic octapeptide derived
       from a conserved, CD4 binding region of gp120, to examine gp120-related
       modulation of lymphocyte signal transduction. Activation of lymphocytes
       through the T cell receptor (TCR) in collaboration with cell surface
       accessory molecules results in rapid increases in tyrosine
       phosphorylation, probably through the recruitment and activation of
       src-family protein tyrosine kinases (PTK) such as lck and fyn which have
       been implicated in mediating the proximal signalling events mediated
       through the TCR. To identify potential mechanisms by which gp120 could
       modulate the function of T lymphocytes, we determined the effect of
       Peptide T on normal, activated peripheral blood lymphoblasts. Treatment
       of normal, activated peripheral blood lymphoblasts with Peptide T
       (10(-9) M) for 60 min transiently reduced levels of protein tyrosine
       phosphorylation (ptyr). Reduction in levels of cellular ptyr was
       associated with transient inhibition of the activity of total cellular
       and CD4-associated p56lck kinase activity (80%). Peptide T also induced
       a small delayed reduction in the p59fyn activity (up to 42%). Despite
       the decrease in total cellular ptyr levels, pp60c-src kinase activity
       was increased 11-fold following treatment with Peptide T. Peptide T
       pretreatment also induced tyrosine phosphorylation of a 48-kD
       CD4-associated protein, indicating that Peptide T may have multiple
       effects. Peptide T did not alter the levels of total cellular p56lck
       enzyme, nor did it directly inhibit the activity of purified p56lck.
       These results are consistent with a Peptide T-dependent modulation of
       PTK regulation, and support the potential of gp120 to interfere with T
       lymphocyte signal transduction in activated T lymphocytes.
 DE    Amino Acid Sequence  CD4-Positive T-Lymphocytes/ENZYMOLOGY  Human
       HIV/*IMMUNOLOGY  HIV Envelope Protein gp120/CHEMISTRY/*PHARMACOLOGY  In
       Vitro  Lymphocyte Transformation  Molecular Sequence Data
       Peptides/CHEMISTRY  Protein-Tyrosine Kinase/*METABOLISM  Proto-Oncogene
       Protein pp60(c-src)/METABOLISM  Proto-Oncogene Proteins/METABOLISM
       Signal Transduction/DRUG EFFECTS  Support, Non-U.S. Gov't
       T-Lymphocytes/ENZYMOLOGY/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).