Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases.
Mast cells play a critical role in IgE-dependent immediate hypersensitivity. Recent studies have shown that, contrary to the traditional view, binding of monomeric IgE to Fc epsilon RI results in a number of biological outcomes in mast cells, including survival. However, IgE molecules display heterogeneity in inducing cytokine production; highly cytokinergic (HC) IgEs cause extensive Fc epsilon RI aggregation, which leads to potent enhancement of survival and other activation events, whereas poorly cytokinergic (PC) IgEs can do so inefficiently. The present study demonstrates that HC, but not PC, IgEs can efficiently induce adhesion and spreading of mouse mast cells on fibronectin-coated plates in slow and sustained kinetics. HC IgE-induced adhesion through beta1 and beta7 integrins promotes survival, IL-6 production, and DNA synthesis. Importantly, we have identified Lyn and Syk as requisite tyrosine kinases and Hck, Btk, and protein kinase C theta as contributory kinases in HC IgE-induced adhesion and spreading, whereas protein kinase C epsilon plays a negative role. Consistent with these results, Lyn, Syk, and Btk are activated in HC IgE-stimulated cells in a slower but more sustained manner, compared with cells stimulated with IgE and Ag. Thus, binding of HC IgEs to Fc epsilon RI induces adhesion of mast cells to fibronectin by modulating cellular activation signals in a unique fashion.
Kitaura
Jiro
J
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Eto
Koji
K
Kinoshita
Tatsuya
T
Kawakami
Yuko
Y
Leitges
Michael
M
Lowell
Clifford A
CA
Kawakami
Toshiaki
T
D000818:Animals; D002448:Cell Adhesion; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism*; D066298:In Vitro Techniques; D039641:Integrin beta Chains / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000276:immunology
D016207:Cytokines; D004792:Enzyme Precursors; D005353:Fibronectins; D039641:Integrin beta Chains; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; C091368:integrin beta7; D007073:Immunoglobulin E; D004247:DNA; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; D011493:Protein Kinase C