Modulation of integrin function in hematopoietic progenitor cells by CD43 engagement: Possible involvement of protein tyrosine kinase and phospholipase C-γ

Naoyuki Anzai, Akihiko Gotoh, Hirohiko Shibayama, Hal E. Broxmeyer

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Attachment of cells to extracellular matrix components is critical for the regulation of hematopoiesis. CD43 is a mucin-like transmembrane sialoglycoprotein expressed on the surface of almost all hematopoietic cells. A highly extended structure of extracellular mucin with negative charge may function as a repulsive barrier to hematopoietic cells. However, some investigators have shown that CD43 has proadhesive properties, and engagement of CD43 has been reported to upregulate integrin-mediated cell adhesion in T cells. We found that cross-linking of CD43 with monoclonal antibodies (MoAbs) enhanced integrin α4β1 (very late antigen [VLA]-4) and α5 β1 (VLA-5)- dependent adhesion of human cord blood CD34+ cells to fibronectin. CD34+ CD38(hi), but not CD34+CD38(-/low) cells responded significantly to the stimulus, suggesting that committed, but not stem and more immature progenitors are sensitive to CD43-mediated activation of integrin. To elucidate the molecular mechanism leading to integrin activation, we used the growth factor-dependent cell line MO7e. Cross-linking of CD43 induced tyrosine phosphorylation of several intracellular molecules including the protein tyrosine kinase Syk, the proto-oncogene product Cbl, and phospholipase C (PLC)-γ2 in MO7e cells. Moreover, protein tyrosine kinase inhibitor herbimycin A and PLC inhibitor U73122 both blocked CD43-induced enhancement of adhesion to fibronectin. These results indicate that signals mediated through CD43 may increase integrin affinity to fibronectin via a pathway dependent on protein tyrosine kinase and PLC-γ activation in hematopoietic progenitors.

Original languageEnglish (US)
Pages (from-to)3317-3326
Number of pages10
JournalBlood
Volume93
Issue number10
DOIs
StatePublished - May 15 1999

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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