Lymphocyte Adaptor Protein (Lnk)

SH2B3 is a key negative regulator of cytokine signaling and plays a critical role in hematopoiesis. Mutations in this gene have been associated with susceptibility to celiac disease type 13 and susceptibility to insulin-dependent diabetes mellitus.Sequence analysis predicted that the 575-amino acid LNK protein contains an N-terminal proline-rich region, a pleckstrin homology (PH) domain, and an Src homology 2 (SH2) domain; the PH and SH2 domains are similar to those of the APS protein. Northern blot analysis detected low expression of a 6.8-kb LNK transcript in various lymphoid cell lines. Confocal fluorescence microscopy showed that the majority of LNK is located in the juxtanuclear region with some found near the plasma membrane.