This proposal is directed towards understanding the structural organization of a large receptor-like, transmembrane enzyme, CD45, that appears to be a prototype for tandem-domain protein tyrosine phosphatase molecules subject to, and participant in, elaborate control mechanisms in living cells. The details of the organization of the molecule will be assessed, largely with modern methods of protein chemistry, in a search for facets of the substructural domains that appear to account for their binding, regulatory and catalytic functions. Particular attention will be given to understanding the importance to regulation of interactions between domains, as well as the modulating effects of reversible phosphorylation on those interactions. This study is focussed on CD45, which provides a vital link in the response of T-cells to antigens in the normal immune response. This transmembrane enzyme, and its homologs in a large family of related enzymes, are also thought to have the potential to act in opposition to growth-promoting factors and certain oncogene products.
