The importance of three membrane-distal tyrosines in the adaptor protein NTAL/LAB.

Journal Article

NTAL (non-T cell activation linker)/LAB (linker for activation of B cells) is a LAT (linker for activation of T cells)-like molecule that is expressed in B cells, mast cells, natural killer cells, and monocytes. Upon engagement of the B cell receptor or Fc receptors, it is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT(-/-) mice. In this study, we utilized various LAB Tyr to Phe mutants to map the phosphorylation and Grb2-binding sites of LAB. We also examined the function of these mutants by investigating their ability to rescue signaling defects in LAT-deficient Jurkat cells and thymocyte development in LAT(-/-) mice. Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.

Full Text

Duke Authors

Cited Authors

  • Koonpaew, S; Janssen, E; Zhu, M; Zhang, W

Published Date

  • March 19, 2004

Published In

Volume / Issue

  • 279 / 12

Start / End Page

  • 11229 - 11235

PubMed ID

  • 14722116

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M311394200

Language

  • eng

Conference Location

  • United States