Signaling and induction of enhanced cytoadhesiveness via the hematopoietic progenitor cell surface molecule CD34.
The transmembrane glycoprotein CD34 shows a highly restricted expression on a crucial subset of hematopoietic cells. We show here that engagement of particular determinants of CD34 can lead to signal transduction and to enhanced adhesiveness of CD34+ hematopoietic cells. Monoclonal antibodies (MoAbs) directed against O-sialoglycoprotease-sensitive epitopes of CD34 (QBEND10, ICH3, BI.3C5, MY10) but not MoAbs against O-sialoglycoprotease-resistant epitopes (9F2, 8G12) induce actin polymerization in KG-1a and KG-1 cells and strongly enhanced cytoadhesiveness. The capacity to induce adhesion requires cellular energy, divalent cations, and intact cytoskeleton but not de novo protein synthesis. The observed cytoadhesion seems at least in part to be caused by a concomitant activation of the beta 2 integrin cytoadhesion pathway. It can be significantly inhibited with lymphocyte function-associated antigen-1 and intercelluar adhesion molecule-1 antibodies. Protein kinase inhibition analyses suggest that the pathways initiated by engagement of the CD34 molecule with certain CD34 MoAbs involves protein tyrosine kinases but that protein kinase C is not critically involved.
Majdic
O
O
Institute of Immunology, University of Vienna, Austria.
Stöckl
J
J
Pickl
W F
WF
Bohuslav
J
J
Strobl
H
H
Scheinecker
C
C
Stockinger
H
H
Knapp
W
W
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34; D002118:Calcium / Q000502:physiology; D002413:Cations, Divalent; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D004734:Energy Metabolism; D000939:Epitopes; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D002413:Cations, Divalent; D015815:Cell Adhesion Molecules; D000939:Epitopes; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D002118:Calcium