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J Biol Chem, Vol. 274, Issue 36, 25291-25296, September 3, 1999
From the Changes in cytosolic calcium concentrations
regulate a wide variety of cellular processes, and calcium-binding
proteins are the key molecules in signal transduction, differentiation,
and cell cycle control. S100A12, a recently described member of the S100 protein family, has been shown to be coexpressed in granulocytes and monocytes together with two other S100 proteins, MRP8 (S100A8) and
MRP14 (S100A9), and a functional relationship between these three S100
proteins has been suggested. Using Western blotting, calcium overlays,
intracellular flow cytometry, and cytospin preparations, we demonstrate
that S100A12 expression in leukocytes is specifically restricted to
granulocytes and that S100A12 represents one of the major
calcium-binding proteins in these cells. S100A12, MRP8, and MRP14
translocate simultaneously from the cytosol to cytoskeletal and
membrane structures in a calcium-dependent manner. However, no evidence for direct protein-protein interactions of S100A12 with
either MRP8 or MRP14 or the heterodimer was found by chemical cross-linking, density gradient centrifugation, mass spectrometric measurements, or yeast two hybrid detection. Thus, S100A12 acts individually during calcium-dependent signaling,
independent of MRP8, MRP14, and the heterodimer MRP8/MRP14. This
granulocyte-specific signal transduction pathway may offer attractive
targets for therapeutic intervention with exaggerated granulocyte
activity in pathological states.
S100A12 Is Expressed Exclusively by Granulocytes and Acts
Independently from MRP8 and MRP14
,,,,
,, and**
Institute of Experimental Dermatology,
Westfälische Wilhelms-Universität Münster,
von-Esmarchstrasse 56, 48149 Münster, Germany, the
¶ Institute of Medical Physics and Biophysics, Westfälische
Wilhelms-Universität Münster, Robert-Koch-Strasse 31, 48149 Münster, Germany, Osiris Therapeutics, Inc.,
Baltimore, Maryland 21231-2001, and the ** Department of
Pediatrics, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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