Vol. 13, Issue 12, 4195-4205, December 2002

Characterization of Human Alpha-Dystrobrevin Isoforms in HL-60 Human Promyelocytic Leukemia Cells Undergoing Granulocytic Differentiation

Agné Kulyte,^* Ruta Navakauskiene, Grazina Treigyte, Arunas Gineitis,^§ Tomas Bergman, and Karl-Eric Magnusson^*

 ^*Division of Medical Microbiology, Linköpings Universitet, SE-581 85 Linköping, Sweden;  Department of Developmental Biology, Institute of Biochemistry, LT-2600 Vilnius, Lithuania;  ^§Department of Biological Chemistry, School of Medicine, University of California at Davis, Davis, California 95616; and  Protein Analysis Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden

The biochemical properties and spatial localization of the protein alpha-dystrobrevin and other isoforms were investigated in cells of the human promyelocytic leukemia line HL-60 granulocytic differentiation as induced by retinoic acid (RA). Alpha-dystrobrevin was detected both in the cytosol and the nuclei of these cells, and a short isoform (gamma-dystrobrevin) was modified by tyrosine phosphorylation soon after the onset of the RA-triggered differentiation. Varying patterns of distribution of alpha-dystrobrevin and its isoforms could be discerned in HL-60 promyelocytes, RA-differentiated mature granulocytes, and human neutrophils. Moreover, the gamma-dystrobrevin isoform was found in association with actin and myosin light chain. The results provide new information about potential involvement of alpha-dystrobrevin and its splice isoforms in signal transduction in myeloid cells during induction of granulocytic differentiation and/or at the commitment stage of differentiation or phagocytic cells.