MITOGEN-ACTIVATED PROTEIN (MAP) KINASE REGULATES PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA AND RELEASE OF ARACHIDONIC-ACID IN MAST-CELLS - INDICATIONS OF COMMUNICATION BETWEEN P38 AND P42 MAP KINASES

Aggregation of the high affinity IgE receptor (Fc epsilon RI) in a mas t cell line resulted in activation of the p42 and the stress-activated p38 mitogen-activated protein (MAP) kinases. Selective inhibition of these respective kinases with PD 098059 and SE 203580 indicated that p 42 MAP kinase, but not p38 MAP kinase, contributed to the production o f the cytokine, tumor necrosis factor a, and the release of arachidoni c acid in these cells. Neither kinase, however, was essential for Fc e psilon RI-mediated degranulation or constitutive production of tumor g rowth factor-beta. Studies with SE 203580 and the p38 MAP kinase activ ator anisomycin also revealed that p38 MAP kinase negatively regulated activation of p42 MAP kinase and the responses mediated by this kinas e.