Reactome | Role of LAT2/NTAL/LAB on calcium mobilization

Role of LAT2/NTAL/LAB on calcium mobilization

Stable Identifier

R-HSA-2730905

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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Role of LAT2/NTAL/LAB on calcium mobilization

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The lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell calcium responses. Both LAT and NTAL are expressed and phosphorylated following engagement of FCERI on mast cells. NTAL is functionally and topographically different from LAT. There is a considerable debate on the role of NTAL in mast cell. Depending on the circumstances, NTAL appears to have a dual role as positive and negative regulator of MC responses elicited via FCERI. Studies conducted in bone marrow-derived mast cells (BMMCs) of mice lacking NTAL displayed enhanced FCERI-mediated tyrosine phosphorylation of several substrates, calcium response, degranulation, and cytokine production. This indicated that NTAL negatively regulates FCERI-mediated degranulation. However, in mice lacking both LAT and NTAL showed severe block in FCERI-mediated signaling than BMMCs deficient in LAT alone, suggesting that NTAL also shares a redundant function with LAT to play a positive role (Draberova et al. 2007, Orr & McVicar. 2011, Zhu et al. 2004, Volna et al. 2004). The major steps in NTAL mediated Ca+2 influx involves NTAL--> GAB2--> PI3K

Literature References

PubMed ID	Title	Journal	Year
17993265	Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells Kovarova, M, Iwaki, S, Charles, N, Rivera, J, Tkaczyk, C, Spicka, J, Metcalfe, DD, Furumoto, Y, Gilfillan, AM, Horejsí, V, Jensen, BM	Cell. Signal.	2008
20643813	LAB/NTAL/Lat2: a force to be reckoned with in all leukocytes? McVicar, DW, Orr, SJ	J. Leukoc. Biol.	2011
17420272	LAT and NTAL mediate immunoglobulin E-induced sustained extracellular signal-regulated kinase activation critical for mast cell survival Malissen, B, Kanagawa, O, Sakuma, M, Cheng, AM, Saito, T, Yamasaki, S, Ishikawa, E	Mol. Cell. Biol.	2007