Recruitment of Tec kinases to p-Slp-76

Stable Identifier
R-MMU-2730850
Type
Reaction [binding]
Species
Mus musculus
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Recruitment of Tec kinases to p-Slp-76
Mast cells express four out of five Tec family members (i.e. BTK, ITK, RLK and TEC) and are activated upon cross-linking of FCERI. They are recruited to the membrane via the interaction of their PH domain with PtdIns(3,4,5)P3 phosphate and their SH2 domain with Y145 of SLP-76 (Kettner et al. 2003). BTK is more important for early response such as phosphorylation of PLC-gamma2 and Ca2+ mobilization, whereas ITK regulates the late responses such as changes in gene expression and cytokine secretion. BTK deficient mice have mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon FCERI cross-linking (Hata et al. 1998). ITK deficient mice have been reported to have reduced MC degranulation and responses to allergic asthma (Forssell et al. 2005). However, Bone marrow derived mast cells (BMMC) derived from ITK deficient mice display a normal degranulation response but secrete elevated level of cytokines (TNFa and IL-13) (Iyer & August 2008). TEC kinase is also one of the crucial regulators of murine mast cell function. TEC is phosphorylated and activated upon FCERI stimulation. TEC deficient bone marrow derived mast cells did not show any in vitro or in vivo defects in histamine release. However, the generation of the leukotriene LTC4 was severely impaired in the absence of TEC (Schmidt et al. 2009).
Literature References
PubMed ID Title Journal Year
9547335 Involvement of Bruton's tyrosine kinase in FcepsilonRI-dependent mast cell degranulation and cytokine production

Nagai, H, Miura, T, Alt, FW, Kawakami, T, Witte, ON, Yao, L, Maeda-Yamamoto, M, Kawakami, Y, Inagaki, N, Han, W, Hata, D, Goldfeld, AE, Hartman, SE, Kitamura, T, Khan, WN, Lantz, CS, Galli, SJ

J. Exp. Med. 1998
16176929 Btk plays a crucial role in the amplification of Fc epsilonRI-mediated mast cell activation by kit

Iwaki, S, Halcomb, K, Tkaczyk, C, Beaven, MA, Metcalfe, DD, Satterthwaite, AB, Gilfillan, AM

J. Biol. Chem. 2005
11279148 Interaction between the Btk PH domain and phosphatidylinositol-3,4,5-trisphosphate directly regulates Btk

Kinet, JP, Scharenberg, AM, Saito, K

J. Biol. Chem. 2001
Participants
Input
Output
Orthologous Events
Recruitment of TEC kinases to p-SLP-76 (Homo sapiens)
Authored
Niarakis, A  (2012-12-21)
Reviewed
Roncagalli, R  (2013-02-13)
Created
Garapati, P V  (2012-12-05)
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