Signal transduction through the beta1 integrin family surface adhesion molecules VLA-4 and VLA-5 of human B-cell precursors activates CD19 receptor-associated protein-tyrosine kinases.
We demonstrate that the CD19 receptor associates with the beta1 family integrin receptors on human B-cell precursors as well as mature B-lymphocytes, and engagement of the beta1 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 beta1 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 though adhesive VLA-4- and VLA-5-mediated contacts.
Xiao
J
J
Signal Transduction Laboratory, University of Minnesota Biotherapy Program, Roseville, 55113, USA.
Messinger
Y
Y
Jin
J
J
Myers
D E
DE
Bolen
J B
JB
Uckun
F M
FM
D018941:Antigens, CD19 / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D015151:Immunoblotting; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000096:biosynthesis / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000502:physiology; D016029:Receptors, Very Late Antigen / Q000502:physiology; D015398:Signal Transduction; D000072377:Syk Kinase
D018941:Antigens, CD19; D004792:Enzyme Precursors; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase