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.
Wange
Ronald L
RL
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
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