p70 phosphorylation and binding to p56lck is an early event in interleukin-2-induced onset of cell cycle progression in T-lymphocytes.
The cytoplasmic protein tyrosine kinase p56lck has been implicated as an effector of interleukin-2-induced cell division in T-lymphocytes, but little is known about physiological substrates for p56lck during these events. We have used p56lck fusion proteins to identify potential cytoplasmic signal transduction proteins that bind to p56lck in mitotically activated human peripheral blood lymphocytes and in constitutively dividing leukemic T-cell lines. In peripheral blood lymphocytes, we have observed an interleukin-2-dependent tyrosine phosphorylation of a 70-kDa protein and binding of tyrosine phosphorylated p70 to the SH2 domain of p56lck. A 70-kDa phosphoprotein was also observed to constitutively bind p56lck in leukemic T-cells. Affinity purification of p56lck-associated p70 and sequencing of proteolytic fragments revealed identity to a 62-kDa protein that has been identified as a ras-GTPase activating protein. These results demonstrate a stimulation-dependent tyrosine phosphorylation of p70 and its interaction with p56lck and may provide a link between p56lck and GTPase-mediated signal transduction pathways in activated T-lymphocytes.
Vogel
L B
LB
CNRS, Station Biologique, Roscoff, France.
Fujita
D J
DJ
D000595:Amino Acid Sequence; D002453:Cell Cycle; D020690:GTPase-Activating Proteins; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)