The missing link(er): a return to symmetry in antigen receptor signaling?

Mol Interv. 2003 Mar;3(2):75-8, 50. doi: 10.1124/mi.3.2.75.

Abstract

B lymphocytes and T lymphocytes utilize several proteins with common functions to transduce signals from their respective receptors. However, at the hierarchial signalling level of SLP-76 [Src homology 2(SH2) domain-containing leukocyte protein of 76-kDa] and LAT (linker for activation of T cells) in T cells, the only corresponding protein in B cells was known to be BLNK (B cell linker protein). It was thought that perhaps BLNK performed the cognate roles of SLP-76 and LAT in B cells; however, mounting evidence to the contrary revealed that this hypothesis was not robust. Two laboratories have recently described the characterization of a protein expressed in B cells and myeloid cells, alternatively termed NTAL (non-T cell activation linker) or LAB (linker for activation of B cells). NTAL/LAB and LAT may have arisen from a primordial gene-duplicating event, but genes that code for the two proteins do not share a very high degree of sequence identity. Wange discusses the results of the two reports, the evidence for functional homology between LAT and NTAL/LAB, and the possibility that the differences between them might lead to specific clinical therapeutics to manipulate immune cell responses.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Phospholipase C gamma
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Receptors, Antigen / metabolism*
  • Signal Transduction*
  • Type C Phospholipases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • B cell linker protein
  • Carrier Proteins
  • LAT protein, human
  • LAT2 protein, human
  • Membrane Proteins
  • Phosphoproteins
  • Receptors, Antigen
  • Type C Phospholipases
  • Phospholipase C gamma