Linker for activation of B cells: a functional equivalent of a mutant linker for activation of T cells deficient in phospholipase C-gamma1 binding.
Adaptor proteins have important functions in coupling stimulation through immunoreceptors with downstream events. The adaptor linker for activation of B cells (LAB)/non-T cell activation linker (NTAL) is expressed in various immune cell types and has a similar domain structure as linker for activation of T cells (LAT). In this study we generated a LAB transgenic mouse to compare the functional differences between LAB and LAT. A LAB transgene expressed in LAT-deficient T cells was able to restore T cell development. However, these mice developed severe organomegaly with disorganized lymphoid tissues. Lymphocytes from these transgenic mice were hyperactivated, and T cells produced large amounts of type II cytokines. In addition, these activities appeared to be uncoupled from the TCR. An examination of the signaling capabilities of these T cells revealed that LAB resembled a LAT molecule unable to bind phospholipase C-gamma1.
Janssen
Erin
E
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Zhu
Minghua
M
Craven
Brandon
B
Zhang
Weiguo
W
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000032:analysis; D002352:Carrier Proteins / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018956:CD5 Antigens; D002352:Carrier Proteins; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D010738:Type C Phospholipases; D051966:Phospholipase C gamma