PMID- 16605127
OWN - NLM
STAT- MEDLINE
DCOM- 20060627
LR  - 20120605
IS  - 1528-2511 (Print)
IS  - 1528-2511 (Linking)
VI  - 271
DP  - 2005
TI  - The role of Src family kinases in mast cell effector function.
PG  - 39-47; discussion 47-53, 95-9
AB  - Src family protein tyrosine kinases (SrcPTK) play a central role in 
      immunoglobulin E (IgE)-mediated activation of mast cells. Functional coupling of 
      the high-affinity IgE receptor (FcepsilonRI) is initiated by the SrcPTK family 
      member, Lyn, through an antigen aggregation-dependent transphosphorylation. 
      Because Lyn is the 'initiating' kinase, an essential role in mast cell effector 
      function was conferred. Recent studies challenge this view. Evidence 
      demonstrating that Lyn kinase is dispensable for mast cell degranulation is now 
      available. In contrast, another SrcPTK family member, Fyn, is required for 
      degranulation and cytokine production. New studies, on mast cells expressing 
      FcepsilonRIbeta ITAM mutants, show that the loss of Lyn interaction with 
      FcepsilonRI has only a modest inhibitory effect on mast cell degranulation and an 
      enhancing effect on lymphokine production, although many of the biochemical 
      signals (including FcepsilonRI phosphorylation) were significantly impaired. In 
      vivo studies on Lyn-null mice also demonstrated that this kinase is a negative 
      regulator of IgE production and anaphylaxis, whereas Fyn kinase is required for 
      anaphylaxis but not for IgE production. Collectively, these studies argue that 
      sustained Lyn kinase activity negatively regulates mast cell responses. This 
      suggests the possible existence of Lyn polymorphisms that may contribute in 
      allergic disease.
FAU - Furumoto, Yasuko
AU  - Furumoto Y
AD  - Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, 
      National Institute of Arthritis and Musculoskeletal and Skin Diseases, National 
      Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Gomez, Gregorio
AU  - Gomez G
FAU - Gonzalez-Espinosa, Claudia
AU  - Gonzalez-Espinosa C
FAU - Kovarova, Martina
AU  - Kovarova M
FAU - Odom, Sandra
AU  - Odom S
FAU - Ryan, John J
AU  - Ryan JJ
FAU - Rivera, Juan
AU  - Rivera J
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - England
TA  - Novartis Found Symp
JT  - Novartis Foundation symposium
JID - 9807767
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.10.2 (Fyn protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
RN  - EC 2.7.10.2 (lyn protein-tyrosine kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Immunoglobulin E/immunology
MH  - Mast Cells/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Protein Isoforms/genetics/immunology
MH  - Proto-Oncogene Proteins c-fyn/genetics/*immunology
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Receptors, IgE/immunology
MH  - Signal Transduction/physiology
MH  - src-Family Kinases/genetics/*immunology
RF  - 37
EDAT- 2006/04/12 09:00
MHDA- 2006/06/28 09:00
CRDT- 2006/04/12 09:00
PHST- 2006/04/12 09:00 [pubmed]
PHST- 2006/06/28 09:00 [medline]
PHST- 2006/04/12 09:00 [entrez]
PST - ppublish
SO  - Novartis Found Symp. 2005;271:39-47; discussion 47-53, 95-9.