This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buzzi, M. Articles by Frackelton, A. R. Search for Related Content PubMed PubMed Citation Articles by Buzzi, M. Articles by Frackelton, A. R., Jr.

Differentiation-induced Changes in Protein-Tyrosine Phosphatase Activity and Commensurate Expression of CD45 in Human Leukemia Cell Lines¹

Department of Medicine, Roger Williams Cancer Center [M. B., L. L., A. J. L., M. R. P., A. R. F.], and Department of BioMedical Sciences, Brown University [D. L. B., A. R. F.], and Division of Clinical Hematology, Rhode Island Hospital [L. D. F.], Providence, Rhode Island 02908

Pharmacologic differentiation of the promyelocytic leukemia HL60 is associated with an increase in cellular tyrosine phosphatase activity. We asked (a) if this increase might, at least in part, be due to changes in a transmembranous protein-tyrosine phosphatase, CD45; and (b) if CD45 changes similarly in other differentiating leukemias. Differentiation of HL60, several chronic myelogenous leukemias, a monocytic leukemia (THP-1), and a monoblastoid leukemia (U-937) could be induced by phorbol ester, 1,25-dihydroxy vitamin D₃, dimethyl sulfoxide, or cyclic AMP analogues. This differentiation was associated with a marked increase in (a) total cellular tyrosine phosphatase activity (2-4-fold as measured by the ability to dephosphorylate a tyrosine-phosphorylated peptide); (b) CD45-specific tyrosine phosphatase activity (2-4-fold); (c) CD45 cell surface expression by flow cytometry (2-5-fold); (d) synthesis of both exon B-dependent M_r 205,000 and exon ABC^- M_r 185,000 CD45 proteins, as revealed by immunoprecipitation with antisera specific for CD45 isoforms. Both isoforms have enhanced electrophoretic mobility when isolated from the differentiated cells. This enhanced mobility did not appear to be due to decreased stoichiometry of CD45 phosphorylation on serine/threonine residues. Interestingly, 12-O-tetradecanoylphorbol-13-acetate transiently reduced CD45 proteintyrosine phosphatase activity in the chronic myelogenous leukemia cell RWLeu4 without altering the CD45 amount (as measured by cell surface immunofluorescence).

Modulation of CD45 tyrosine phosphatase activity (and protein levels) may play a role in differentiation or in maintaining cells in a nonproliferative state or may represent a phenotypic marker of differentiation.

¹ Supported in part by National Cancer Institute Cancer Center Grant P30-CA13943-18, by National Cancer Institute Grant RO1-CA39235 (A. R. F.) and by a grant from the Italian Association of Cancer Research (M. B.).

² Present address: Institute of Hematology, University of Bologna, Bologna, Italy.

³ M. B. and L. L. contributed equally to this work.

⁴ Present address: Department of Medicine, New England Deaconess Hospital, Boston, MA.

⁵ To whom requests for reprints should be addressed, at Department of Medicine, Roger Williams General Hospital, Providence, RI 02908.

Received 2/ 6/92. Accepted 5/ 7/92.

This article has been cited by other articles:

				H. Kubagawa, S. Oka, Y. Kubagawa, I. Torii, E. Takayama, D.-W. Kang, G. L. Gartland, L. F. Bertoli, H. Mori, H. Takatsu, et al. Identity of the elusive IgM Fc receptor (Fc{micro}R) in humans J. Exp. Med., November 23, 2009; 206(12): 2779 - 2793. [Abstract] [Full Text] [PDF]

				M.-F. Lin, T.-C. Meng, P. S. Rao, C. Chang, A. H. Schonthal, and F.-F. Lin Expression of Human Prostatic Acid Phosphatase Correlates with Androgen-stimulated Cell Proliferation in Prostate Cancer Cell Lines J. Biol. Chem., March 6, 1998; 273(10): 5939 - 5947. [Abstract] [Full Text] [PDF]

				M.-C. Wang, J. H. Liu, and F.-F. Wang Protein Tyrosine Phosphatase-Dependent Activation of beta -Globin and delta -Aminolevulinic Acid Synthase Genes in the Camptothecin-Induced IW32 Erythroleukemia Cell Differentiation Mol. Pharmacol., April 1, 1997; 51(4): 558 - 566. [Abstract] [Full Text]

				M. P. Ramprasad, V. Terpstra, N. Kondratenko, O. Quehenberger, and D. Steinberg Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein PNAS, December 10, 1996; 93(25): 14833 - 14838. [Abstract] [Full Text] [PDF]