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Activation of RBL-2H3 mast cells is dependent on tyrosine phosphorylation of phospholipase D2 by Fyn and Fgr

Authors
 Wahn Soo Choi  ;  Takaaki Hiragun  ;  Michael A. Beaven  ;  Jeung Whan Han  ;  Erk Her  ;  Ahmed Chahdi  ;  Hyoung-Pyo Kim  ;  Young Mi Kim  ;  Jun Ho Lee 
Citation
 MOLECULAR AND CELLULAR BIOLOGY, Vol.24(16) : 6980-6992, 2004 
Journal Title
MOLECULAR AND CELLULAR BIOLOGY
ISSN
 0270-7306 
Issue Date
2004
MeSH
Animals ; Cell Line ; EnzymeActivation ; Enzyme Inhibitors/metabolism ; Humans ; MastCells/cytology ; MastCells/immunology ; MastCells/physiology* ; PhospholipaseD/genetics ; PhospholipaseD/metabolism* ; Phosphorylation ; Point Mutation ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism* ; Proto-Oncogene Proteins c-fyn ; Pyrimidines/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Rats ; Receptors, IgE/immunology ; Tyrosine/metabolism* ; Vanadates/chemistry ; Vanadates/metabolism ; src-Family Kinases/genetics ; src-Family Kinases/metabolism*
Abstract
Both phospholipase D1 (PLD1) and PLD2 regulate degranulation when RBL-2H3 cells are stimulated via the immunoglobulin E receptor, FcɛRI. However, the activation mechanism for PLD2 is unclear. As reported here, PLD2 but not PLD1 is phosphorylated through the Src kinases, Fyn and Fgr, and this phosphorylation appears to regulate PLD2 activation and degranulation. For example, only hemagglutinin-tagged PLD2 was tyrosine phosphorylated in antigen-stimulated cells that had been made to express HA-PLD1 and HA-PLD2. This phosphorylation was blocked by a Src kinase inhibitor or by small interfering RNAs directed against Fyn and Fgr and was enhanced by overexpression of Fyn and Fgr but not by other Src kinases. The phosphorylation and activity of PLD2 were further enhanced by the tyrosine phosphatase inhibitor, Na3VO4. Mutation of PLD2 at tyrosines 11, 14, 165, or 470 partially impaired, and mutation of all tyrosines blocked, PLD2 phosphorylation and activation, although two of these mutations were detrimental to PLD2 function. PLD2 phosphorylation preceded degranulation, both events were equally sensitive to inhibition of Src kinase activity, and both were enhanced by coexpression of PLD2 and the Src kinases. The findings provide the first description of a mechanism for activation of PLD2 in a physiological setting and of a role for Fgr in FcɛRI-mediated signaling.
Files in This Item:
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DOI
10.1128/MCB.24.16.6980-6992.2004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/112945
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