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The Journal of Immunology, Vol 151, Issue 4 1979-1988, Copyright © 1993 by American Association of Immunologists
ARTICLES |
EY Lin, A Orlofsky, MS Berger and MB Prystowsky
Biology graduate Group, School of Arts and Sciences, University of Pennsylvania, Philadelphia 19104.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoietic cell proliferation, differentiation, and functional activation by inducing the expression of specific genes. As part of an investigation of the regulation of gene expression by GM-CSF, we have previously identified a novel murine GM-CSF-inducible gene, A1. In this report, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression pattern of the gene. The results demonstrate that A1 is a hemopoietic tissue-specific gene that is expressed in several hemopoietic cell lineages, including T-helper lymphocytes, macrophages, and neutrophils. In murine bone marrow-derived macrophages, A1 gene expression is rapidly and transiently induced by GM-CSF, and the induction was independent of de novo protein synthesis. In addition to GM-CSF, a transient induction of A1 mRNA accumulation was observed in response to LPS in macrophages. This induction is not mediated by IL-1 alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 gene expression is stably induced during granulocyte colony-stimulating factor-stimulated myeloid cell differentiation. The A1 message encodes a predicted polypeptide with an M(r) of 20,024 and no signal peptide. The peptide sequence contains a region of 80 amino acids that shows similarity to bcl-2 and to the recently described bcl-2-related gene, MCL1. These data demonstrate that A1 is a novel early-response gene whose expression is associated with a variety of stimuli and occurs in several hemopoietic cell types.
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G. M. Feldman, L. A. Rosenthal, X. Liu, M. P. Hayes, A. Wynshaw-Boris, W. J. Leonard, L. Hennighausen, and D. S. Finbloom STAT5A-Deficient Mice Demonstrate a Defect in Granulocyte-Macrophage Colony-Stimulating Factor-Induced Proliferation and Gene Expression Blood, September 1, 1997; 90(5): 1768 - 1776. [Abstract] [Full Text] [PDF]
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C. Thompson Apoptosis in the pathogenesis and treatment of disease Science, March 10, 1995; 267(5203): 1456 - 1462. [Abstract] [PDF]
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