A common signaling pathway via Syk and Lyn tyrosine kinases generated from capping of the sialomucins CD34 and CD43 in immature hematopoietic cells.
The sialomucin CD34 is a useful marker for hematopoietic stem/progenitor cells. However, the role of CD34 remains poorly understood. Here we investigate the functions of CD34 and another sialomucin CD43 coexpressed on hematopoietic stem/progenitor cells. Stimulation of undifferentiated hematopoietic KG1a cells with anti-CD34 or anti-CD43 induced homotypic cytoadhesion, accompanied by formation of a long-lived cap of CD34 and CD43 respectively, which colocalized with F-actin. Stimulation with either antibody specifically increased tyrosine phosphorylation of the identical set of proteins of Lyn, Syk, pp60, pp69, and pp77 at the capping site. These events were similar to those observed in monocytic U937 cells ectopically expressing CD34. After stimulation of KG1a cells, coimmunoprecipitation of Lyn with pp69 and pp77 and of Syk with pp37 was detected in the membrane fraction. Blockade of antibody-induced cap formation by treatment with cytochalasin D leads to inhibition of tyrosine phosphorylation of Syk and pp77 and homotypic cytoadhesion. Moreover, normal human CD34(+) bone marrow cells showed cap formation of CD34 or CD43 after stimulation. These results suggest that crosslinking of either CD34 or CD43 activates the same signaling pathway for cytoadhesion through Lyn, Syk, and the novel tyrosine-phosphorylated proteins within hematopoiesis.
Tada
J
J
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto, Japan.
Omine
M
M
Suda
T
T
Yamaguchi
N
N
D015703:Antigens, CD; D018952:Antigens, CD34 / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D004792:Enzyme Precursors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051917:Leukosialin; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011940:Receptor Aggregation / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D019061:src-Family Kinases / Q000502:physiology*
D015703:Antigens, CD; D018952:Antigens, CD34; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases