Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation.
Fc epsilon RI activation of mast cells is thought to involve Lyn and Syk kinases proximal to the receptor and the signaling complex organized by the linker for activation of T cells (LAT). We report here that Fc epsilon RI also uses a Fyn kinase-dependent pathway that does not require Lyn kinase or the adapter LAT for its initiation, but is necessary for mast cell degranulation. Lyn-deficiency enhanced Fyn-dependent signals and degranulation, but inhibited the calcium response. Fyn-deficiency impaired degranulation, whereas Lyn-mediated signaling and calcium was normal. Thus, Fc epsilon RI-dependent mast cell degranulation involves cross-talk between Fyn and Lyn kinases.
Parravicini
Valentino
V
Molecular Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA.
Gadina
Massimo
M
Kovarova
Martina
M
Odom
Sandra
S
Gonzalez-Espinosa
Claudia
C
Furumoto
Yasuko
Y
Saitoh
Shinichiroh
S
Samelson
Lawrence E
LE
O'Shea
John J
JJ
Rivera
Juan
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology*; D003433:Crosses, Genetic; D004792:Enzyme Precursors / Q000276:immunology; D005260:Female; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000276:immunology*; D051076:Proto-Oncogene Proteins c-fyn; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004792:Enzyme Precursors; C490897:Gab1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases