Document 0820
 DOCN  M95A0820
 TI    The CD4-associated tyrosine kinase p56lck is required for lymphocyte
       chemoattractant factor-induced T lymphocyte migration.
 DT    9510
 AU    Ryan TC; Cruikshank WW; Kornfeld H; Collins TL; Center DM; Pulmonary
       Center, Boston University School of Medicine,; Massachusetts 02118, USA.
 SO    J Biol Chem. 1995 Jul 21;270(29):17081-6. Unique Identifier : AIDSLINE
       MED/95340485
 AB    Lymphocyte chemoattractant factor (LCF) is a polypeptide cytokine which
       induces both cell motility and activation of T lymphocytes. These
       LCF-induced events demonstrate an absolute requirement for the cell
       surface expression of CD4. Because many CD4-mediated T lymphocyte
       activation events have been demonstrated to require the association of
       the src-related tyrosine kinase p56lck with the cytoplasmic domain of
       CD4, we examined the role of p56lck in LCF-induced lymphocyte migration
       in a murine T cell hybridoma line expressing transfected human CD4. LCF
       induces the catalytic activity of CD4 associated p56lck at
       chemoattractant concentrations of cytokine. Hybridoma cells that express
       CD4 with cytoplasmic point mutations which uncouple the CD4-lck
       association lack both lck enzymatic activity and chemotactic responses
       to LCF. The enzymatic activity of lck however does not appear to be
       required for CD4-mediated migratory signal. First, the protein tyrosine
       kinase inhibitor herbimycin A blocked LCF-induced p56lck activation but
       had no effect on the LCF-induced motile response. Second, T cell
       hybridomas expressing a chimeric receptor combining the extracellular
       domain of human CD4 and murine p56lck which lacked the kinase domain had
       a normal LCF-induced motile response. We conclude from these
       observations that CD4-lck coupling is essential for LCF-induced T
       lymphocyte migration but the motile response is independent of the
       enzymatic activity of CD4-associated p56lck.
 DE    Animal  Antigens, CD4/*PHYSIOLOGY  Cell Line  Cell Movement/DRUG EFFECTS
       Chemotactic Factors/*PHARMACOLOGY  Chimeric Proteins/PHARMACOLOGY  HIV
       Envelope Protein gp120/PHYSIOLOGY  Lymphokines/*PHARMACOLOGY  Mice
       Phosphorylation  Protein-Tyrosine Kinase/*PHYSIOLOGY
       Quinones/PHARMACOLOGY  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/*PHYSIOLOGY  JOURNAL ARTICLE

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