Activation and signal transduction via mitogen-activated protein (MAP) kinases in T lymphocytes

The various mitogen-activated protein (MAP) kinases have central roles in the signalling pathways of T lymphocytes. Their activation is uniquely dependent on dual phosphorylation of a serine/threonine and a tyrosine residue and is regulated by several levels of kinases in parallel cascades. In addition, both the MAP kinases and their upstream, activating kinases are regulated by several phosphatases. Although each of the MAP kinases have many cytoplasmic substrates, their ability to translocate to the nucleus means that they can transmit signals from the cytoplasm directly to transcription factors, which are sometimes nuclear bound. The MAP kinase cascades are activated in T lymphocytes by a variety of different external stimuli. They play an important role in transducing both the signal from T cell receptor and costimulatory molecules, on the T cell surface, and are able to regulate several of the transcription factors controlling the expression of critical genes, including that for IL-2. This review examines how the activation of several MAP kinases is regulated, their role in signal transduction initiated by a variety of stimuli, and how this may lead to different cellular responses.