Roles of a conserved family of adaptor proteins, Lnk, SH2-B, and APS, for mast cell development, growth, and functions: APS-deficiency causes augmented degranulation and reduced actin assembly.
Lnk, SH2-B, and APS form a conserved adaptor protein family. All of those proteins are expressed in mast cells and their possible functions in signaling through c-Kit or FcRI have been speculated. To investigate roles of Lnk, SH2-B or APS in mast cells, we established IL-3-dependent mast cells from Ink-/-, SH2-B-/-, and APS -/- mice. IL-3-dependent growth of those cells was comparable. Proliferation or adhesion mediated by c-Kit as well as degranulation induced by cross-linking FcRI were normal in the absence of Lnk or SH2-B. In contrast, APS-deficient mast cells showed augmented degranulation after cross-linking FcRI compared to wild-type cells, while c-Kit-mediated proliferation and adhesion were kept unaffected. APS-deficient mast cells showed reduced actin assembly at steady state, although their various intracellular responses induced by cross-linking FcRI were indistinguishable compared to wild-type cells. Our results suggest potential roles of APS in controlling actin cytoskeleton and magnitude of degranulation in mast cells.
Kubo-Akashi
Chiyomi
C
Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639, Japan.
Iseki
Masanori
M
Kwon
Sang-Mo
SM
Takizawa
Hitoshi
H
Takatsu
Kiyoshi
K
Takaki
Satoshi
S
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D002469:Cell Separation; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D015151:Immunoblotting; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D017455:Receptors, IgE / Q000737:chemistry; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013997:Time Factors
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D016207:Cytokines; D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; C490777:Lnk protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D018121:Receptors, Cytokine; D017455:Receptors, IgE; C518910:SH2B1 protein, human; C492010:SH2B1 protein, rat; C490778:SH2B3 protein, human; C488161:Sh2b2 protein, mouse; C488162:Sh2b2 protein, rat; C115327:Sh2bpsm1 protein, mouse; D013844:Thiazoles; D053778:Thiazolidines; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C037067:latrunculin A; D002118:Calcium