Lipopolysaccharide induces activation of CD14-associated protein tyrosine kinase p53/56lyn.
Bacterial lipopolysaccharide (LPS) induces a pleiotropic activation of the immune system which might subsequently result in septic shock. One of the cell surface receptors for LPS is the glycophosphatidylinositol-anchored protein CD14. Binding of LPS to CD14 induces production of lymphokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-8, and CD14 is subsequently released from the cell surface. However, the mechanism of signaling via CD14 is still not known. We report here that protein tyrosine kinase (PTK) p56lyn is coupled to the LPS receptor CD14 in human monocytes. LPS rapidly activates CD14-associated p56lyn simultaneously with PTKs p58hck and p59c-fgr. Inhibition of PTKs by herbimycin A completely blocks LPS-induced down-modulation of CD14 and production of TNF-alpha and IL-1. These data suggest a critical role of PTKs in the LPS/CD14-mediated signal transduction pathway in human monocytes.
Stefanová
I
I
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Corcoran
M L
ML
Horak
E M
EM
Wahl
L M
LM
Bolen
J B
JB
Horak
I D
ID
D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis; D009000:Monocytes / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019061:src-Family Kinases
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008222:Lymphokines; D011505:Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases