CD45 phosphotyrosine phosphatase and p56/ck protein tyrosine kinase: a functional complex crucial in T cell signal transduction

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Abstract
Tyrosine phosphorylation of several intracellular proteins is observed very early during T cell activation. p56lck, a non-receptor src-like protein tyrosine kinase (PTK) which is associated with the intracellular domains of CD4 and CD8 co-receptors, has been implicated in these early signal transduction events. Furthermore, recent experiments Indicate that the receptor phosphotyrosine phosphatase, CD45, might be important in the regulation of p56/ck PTK activity and that Its expression is required for the generation of second messenger molecules following TCR triggering. Here, using co-capping experiments and double indirect Immunofluorescence microscopy In functional human T lymphocytes, a specific co-distribution of a significant fraction of p56/ck with CD45, but not with several other cell surface proteins, has been revealed. This is the first demonstration of a physical Interaction between a receptor phosphotyrosine phosphatase and a PTK under physiologically relevant conditions. In addition, after antibody-Induced capping of CD4, both a co-localization of p56/ck and CD4, and concomitantly a significant increase in Intracellular phosphotyrosine at the sites of CD4 caps were observed. In strong contrast to these results, co-clustering of CD4 with CD45 did not result in any detectable intracellular phosphotyrosine at the cap sites. These data Indicate that CD45 can act on CD4-assoclated phosphoproteins in viable human T lymphocytes. Further, this provides evidence that p56/ck PTK is a substrate of CD45 phosphotyrosine phosphatase in vivo and thereby supports the idea that CD45 is an early regulator of T cell activation involved in the modulation of the coupling of receptor-triggered events to intracellular signalling pathways.

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