Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells.
Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in signaling through the high-affinity IgE receptor (FcepsilonRI) using WASP-deficient mice. IgE-dependent degranulation and cytokine secretion were markedly diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream signaling events that include FcepsilonRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cgamma and Ca(2+) mobilization were diminished. IgE-dependent activation of c-Jun N-terminal kinase, cell spreading and redistribution of cellular F-actin in mast cells were reduced in the absence of WASP. We conclude that WASP regulates FcepsilonRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.
Pivniouk
Vadim I
VI
Division of Immunology, Children's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Snapper
Scott B
SB
Kettner
Alexander
A
Alenius
Harri
H
Laouini
Dhafer
D
Falet
Hervé
H
Hartwig
John
J
Alt
Frederick W
FW
Geha
Raif S
RS
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D022081:Cell Surface Extensions / Q000187:drug effects; D004140:Dinitrophenols / Q000276:immunology / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006632:Histamine / Q000097:blood; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis; D051966:Phospholipase C gamma; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011940:Receptor Aggregation / Q000276:immunology; D017455:Receptors, IgE / Q000378:metabolism / Q000502:physiology*; D012709:Serum Albumin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000199:Actins; D004140:Dinitrophenols; D007377:Interleukin-3; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; C495768:Was protein, mouse; C495772:Wasl protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C058064:dinitrophenyl-human serum albumin conjugate; D007073:Immunoglobulin E; D006632:Histamine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D001619:beta-N-Acetylhexosaminidases; D002118:Calcium