IN-VIVO ASSOCIATION BETWEEN P56(LCK) AND MAP KINASE DURING IL-2-MEDIATED LYMPHOCYTE-PROLIFERATION

We previously reported that p56(Ick) expression is upregulated in huma n B lymphocytes upon mitogenic stimulation, In this report, we charact erized the molecules associated with p56(Ick) in vivo in leukemic B ce lls costimulated with anti-mu AB and IL-2 for 72 h, In vitro phosphory lation after p56(Ick) immunoprecipitation indicated that p56(Ick) is a ssociated in vivo with the beta chain of the IL-2 receptor and p42 MAP kinase as well as a number of other proteins, Moreover, p56(Ick)-asso ciated MAP kinase is tyrosine and threonine phosphorylated, suggesting that it is activated, Prevention of DNA synthesis with aphidicolin ab rogated this molecular association, and furthermore, cell cycle analys is with IL-2-dependent T cells showed that in cells in C-1, MAP kinase was not associated to p56(Ick), whereas this p56(Ick)-MAP kinase asso ciation was observed when cells are in S phase, Thus, p56(Ick) and MAP kinase are only associated during S phase. These data suggest that MA P kinase in association with p56(Ick) is directly involved in the cont rol of IL-2-mediated PNA synthesis of both B and T lymphocytes,