The missing link(er): a return to symmetry in antigen receptor signaling?
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.
Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, MSC-12, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. wanger@grc.nih.nia.gov
Ronald L
RL
Wange
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011946:Receptors, Antigen / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C113939:B cell linker protein; D002352:Carrier Proteins; C110810:LAT protein, human; C419196:LAT2 protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D011946:Receptors, Antigen; D010738:Type C Phospholipases; D051966:Phospholipase C gamma