Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases

The dynamic regulation of protein tyrosine phosphorylation is crucial for a number of cellular processes including cell growth, differentiation, migration, and death. It thus represents a powerful control point for integration of environmental signals into cellular responses. Regulation of tyrosine phosphorylation is determined by the balance between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). In the immune system, precise and coordinated regulation of this equilibrium allows for rapid responses to foreign antigens, whereas an imbalance between PTKs and PTPs can have pathologic consequences, including autoimmunity, immunodeficiency, and malignancy (1). In this review, we highlight recent advances in our understanding of key PTKs and PTPs that play critical roles in modulating cellular levels of phosphotyrosine in resting T cells, during T cell activation, and during downregulation of an immune response.