Signal transduction through the β1 integrin family surface adhesion molecules VLA-4 and VLA-5 of human B-cell precursors activates CD 19 receptor-associated protein-tyrosine kinases

Abstract

We demonstrate that the CD19 receptor associates with the β1 family integrin receptors on human B-cell precursors as well as mature B-lymphocytes, and engagement of the β1 family integrin receptors with monoclonal antibody homoconjugates leads to rapid activation of the CD19-associated protein-tyrosine kinases (PTK) and results in hyperphosphorylation of CD19 on tyrosine residues. Our findings prompt the hypothesis that homoconjugate-induced integrin clustering may effect the approximation and, by intermolecular cross-phosphorylation, activation of the CD19-associated PTK and subsequent tyrosine phosphorylation of the CD19 receptor. The ability of the β1 family integrin receptors to transmit a biochemical signal triggering the CD19-linked multifunctional PTK pathway provides a possible explanation for the pleiotropic biologic responses generated through adhesive VLA-4- and VLA-5-mediated contacts.