liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Characterization of Human Alpha-Dystrobrevin Isoforms in HL-60 Human Promyelocytic Leukemia Cells Undergoing Granulocytic Differentiation
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Department of Developmental Biology, Institute of Biochemistry, Vilnius, Lithuania.
Department of Developmental Biology, Institute of Biochemistry, Vilnius, Lithuania.
Department of Biological Chemistry, School of Medicine, University of California at Davis, Davis, California.
Show others and affiliations
2002 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 13, no 12, 4195-4205 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2002. Vol. 13, no 12, 4195-4205 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26511DOI: 10.1091/mbc.E02-03-0128Local ID: 11068OAI: oai:DiVA.org:liu-26511DiVA: diva2:247060
Note

On the day of the defence day the status of this article was submitted.

Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
In thesis
1. New aspects on retinoic acid induced HL-60 granulocytic differentiation
Open this publication in new window or tab >>New aspects on retinoic acid induced HL-60 granulocytic differentiation
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The underlying mechanisms of myeloid cell differentiation are still not entirely elucidated. It is therefore an urgent task to extent the basis for a comprehensive model of granulocytes differentiation. A primary goal for studies has been the identification of differentiation markers. These often correspond to genes that are expressed at defined steps during the differentiation process or in the fully differentiated phenotype. Here is demonstrated that the program of phenotype formation entails dramatic changes in long-term tyrosine phosphorylation of some cytoplasmic proteins during retinoic acid (RA)-induced HL-60 cell differentiation to granulocytes. A significant increase in the phosphotyrosine content of a kinase (Erk2) in the commitment and terminal stages of HL-60 cell differentiation (48-120 h) was related to promotion of cell survival and triggering of apoptosis. In addition, some cytosolic proteins of apoptotic origin were delineated in the differentiating population. The pattern of tyrosine phosphorylations of specific cytosolic proteins in maturing and apoptotic granulocytes should be a powerful tool for further elucidation of differentiation mechanisms. We developed a new approach based on cytosolic protein tagging and nuclear import analysis combined with assessment of specific protein tyrosine phosphorylations by two-dimensional gel electrophoresis. Many of the genes involved in the differentiation of multipotent stem cells to specific cellular lineages are still unknown. Accordingly, we searched for additional tyrosine phosphorylated, RA-induced transcription regulators that are translocated into the nucleus during commitment of HL-60 cells to become granulocyte-like cells. It is shown, that transcription factors required for lineage commitment of differentiating (C/EBPß, c-myb) and for survival of differentiated cells (STATs, NFKB) co-operatively promoted signaling in the HL-60 cell line in response to RA. Identification of the tyrosine-phosphorylated proteins being translocated into the nucleus during HL-60 cell differentiation was our further goaL This way, we show for the first time that human gamma~dystrobrevin is expressed in promyelocytic HL-60 cell line. We detected gamma-dystrobrevin in the cytosol and the nuclei of these cells, and, in the latter location; it was modified by tyrosine phosphorylation soon after the onset of the RA-triggered differentiation. Varying patterns of distribution of gamma-dystrobrevin could be discerned in HL-60 promyelocytes, RA-differentiated mature granulocytes, and hwnan neutrophils. Moreover, we found gamma-dystrobrevin in association with actin and myosin light chain. Our results provide new information about potential involvement of gamma-dystrobrevin in signal transduction in myeloid cells during induction of granulocytic differentiation and/or at the commitment stage of differentiation or phagocytic cells. In addition, our study confirms and extends knowledge about the genes involved in granulocytic differentiation and growth arrest. This shuiy corroborates the value of cDNA RDA to isolate factors involved in myeloid maturation. In conclusion, the more detailed analysis of granulocytic differentiation of HL-60 cells presented here provides new data that should allow further refinement of models of myeloid differentiation.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2002. 119 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 723
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26659 (URN)11225 (Local ID)91-7373-165-X (ISBN)11225 (Archive number)11225 (OAI)
Public defence
2002-04-11, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Navakauskiene, RutaMagnusson, Karl-Eric

Search in DiVA

By author/editor
Navakauskiene, RutaMagnusson, Karl-Eric
By organisation
Medical MicrobiologyFaculty of Health Sciences
In the same journal
Molecular Biology of the Cell
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 49 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf