S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14.
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.
Vogl
T
T
Institute of Experimental Dermatology, Westfälische Wilhelms-Universität Münster, von-Esmarchstrasse 56, 48149 Münster, Germany. vogl@uni-muenster.de
Pröpper
C
C
Hartmann
M
M
Strey
A
A
Strupat
K
K
van den Bos
C
C
Sorg
C
C
Roth
J
J
D000943:Antigens, Differentiation / Q000378:metabolism*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D040501:Calgranulin A; D040502:Calgranulin B; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D009928:Organ Specificity; D009418:S100 Proteins / Q000378:metabolism*; D000067616:S100A12 Protein
D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human