CD45 is a family of high molecular weight leukocyte cell surface glycoproteins. Recently, two related subregions ofthe cytoplasmic domain ofCD45 have been shown to have 3040% amino acid identity with a human placental protein phosphotyrosine phosphatase, and CD45 isolated from human spleen was found to exhibit intrinsic protein phosphotyrosine phosphatase (EC 3.1.3.48) activity. In the present studies, we demonstrate that each of the known isoforms of murine CD45 has an equivalent basal level of protein phosphotyrosine phosphatase activity and establish that this enzymatic activity is associated with the cytoplasmic domain of the glycoprotein. Studies with three independent sets of wellcharacterized parental CD45+, mutant CD45-, and revertant CD45+ lymphoma cell lines indicate that loss of CD45 increases the phosphorylation of the src-related leukocyte-specific tyrosine protein kinase p56Ick on tyrosine-505, a putative negative regulatory site. This suggests that CD45 may play a role in leukocyte growth regulation by altering the kinase activity of ps6ck.CD45 (T200 or L-CA) is a family of major leukocyte-specific cell surface glycoproteins expressed exclusively-on hematopoietic cells (reviewed in ref. 1). Isoforms of CD45 are generated by the alternative splicing of three exons, each encoding '50 amino acids that are inserted near the amino terminus of the molecule. Of the eight possible mRNAs that can be generated by the differential use ofthe three exons, six have been identified by sequencing CD45 cDNAs from mouse, human, and rat (2-6). The extra sequences of CD45 encoded by the alternatively spliced exons contain multiple sites for O-linked oligosaccharides, and at least one extra segment is known to be extensively glycosylated (7). Different isoforms of CD45 are selectively expressed on specific subpopulations of hematopoietic cells, and changes in the pattern of expression of CD45 isoforms in T cells also occur upon antigenic stimulation (8-10). CD45 is also distinguished by a large, highly conserved, cytoplasmic domain of 705 amino acids that can be subdivided into two related subdomains of '300 amino acids. Recently, each of these subdomains was shown to have 30-40% amino acid identity with a soluble human placental protein phosphotyrosine phosphatase (PTPase; protein-tyrosine phosphatase, EC 3.1.3.48), and CD45 isolated from human spleen was found to have intrinsic PTPase activity (11,12). We have extended these observations by analyzing the PTPase activity of individual isoforms of murine CD45 and truncated forms of the molecule. Further, the availability of three independent sets of parental CD45+, mutant CD45-, and revertant CD45+ lymphoma cells has allowed us to search for in vivo substrates of the CD45 PTPase activity by comparing the phosphotyrosine-containing proteins in CD45' and CD45-cells. The results ofthis analysis indicate that loss of CD45 in the mutant lymphoma cells correlates with increased phosphorylation of the src-related leukocyte-specific tyrosine protein kinase p56Ick (13...

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Some human B-lymphoblastoid cell lines are shown to express at least two types ofIa-like antigens. One antigen is defined by alloantisera to HLA-DR, and the other antigen is defined by alloantisera and a monoclonal antibody to the specificities DC1, MT1 (MB1), and LB12, which are in linkage disequilibrium with HLA-DR. The subunits of the DC1 molecule differ from those of the DR molecule. The light chains of both molecules are structurally polymorphic.