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Review
, 39 (5), 868-73

Ntal/Lab/Lat2

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Review

Ntal/Lab/Lat2

Shoko Iwaki et al. Int J Biochem Cell Biol.

Abstract

Non-T cell activation linker (NTAL)/linker for activation of B cells (LAB), now officially termed LAT2 (linker for activation of T cells 2) is a 25-30kDa transmembrane adaptor protein (TRAP) associated with glycolipid-enriched membrane fractions (GEMs; lipid rafts) in specific cell types of hematopoietic lineage. Tyrosine phosphorylation of NTAL/LAB/LAT2 is induced by FcvarepsilonRI aggregation and Kit dimerization in mast cells, FcgammaRI aggregation in monocytes, and BCR aggregation in B cells. NTAL/LAB/LAT2 is also expressed in resting NK cells but, unlike the related TRAP, LAT, not in resting T cells. As demonstrated in monocytes and B cells, phosphorylated NTAL/LAB/LAT2 recruits signaling molecules such as Grb2, Gab1 and c-Cbl into receptor-signaling complexes. Although gene knock out and knock down studies have indicated that NTAL/LAB/LAT2 may function as both a positive and negative regulator of mast cell activation, its precise role in the activation of these and other hematopoietic cells remains enigmatic.

Figures

Figure 1
Figure 1
Representation of the structure and location of human NTAL/LAB/LAT2. The striped triangle designates the position of the juxtamembrane palmitoylation site, and the open triangles designate the position of the potential tyrosine phosphorylation sites.
Figure 2
Figure 2
Simplified representation of the potential roles of NTAL/LAB/LAT2 in FcεRI-mediated mast cell degranulation. In this figure, the positively regulated pathways are represented by green arrows, and the negative pathways by red arrows. FcεRI-aggregation leads to activation of the tyrosine kinases, Lyn and Syk, which subsequently phosphorylate LAT and NTAL/LAB/LAT2. LAT regulates degranulation by recruiting cytosolic adaptor molecules and phospholipase (PL)Cγ1 thereby increasing calcium flux in a PLCγ1-dependent manner. NTAL/LAB/LAT2 appears to regulate both negative and positive pathways for the regulation of degranulation, however, the molecules regulating these responses are currently unknown. Nevertheless, it has been proposed that the positive pathway may involve activation of PI3K. For further details and discussions of this pathway, please refer to Gilfillan & Tkaczyk (2006).

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