Syk is required for integrin signaling in neutrophils.
The Syk tyrosine kinase plays a critical role in the signaling machinery of various receptors of the adaptive immune system. Here we show that Syk is also an essential component of integrin signaling in neutrophils. syk(-/-) neutrophils failed to undergo respiratory burst, degranulation, or spreading in response to proinflammatory stimuli while adherent to immobilized integrin ligands or when stimulated by direct crosslinking of integrins. Signaling from the beta(1), beta(2), or beta(3) integrins was defective in syk(-/-) cells. Syk colocalized with CD18 during cell spreading and initiated downstream signaling events leading to actin polymerization. Surprisingly, these defects in integrin-mediated activation did not impair the integrin-dependent in vitro or in vivo migration of syk(-/-) neutrophils or of cells deficient in Src-family kinases. Thus, integrins use different signaling mechanisms to support migration and adherent activation.
Mócsai
Attila
A
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
Zhou
Meijuan
M
Meng
Fanying
F
Tybulewicz
Victor L
VL
Lowell
Clifford A
CA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D019012:Integrin beta1 / Q000378:metabolism*; D039661:Integrin beta3; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D000072377:Syk Kinase
D015703:Antigens, CD; D018821:CD18 Antigens; D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; D019012:Integrin beta1; D039661:Integrin beta3; D047908:Intracellular Signaling Peptides and Proteins; D010980:Platelet Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse