Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL.
Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcepsilonRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcepsilonRI-mediated signaling than LAT(-/-) mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcepsilonRI-mediated signaling.
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Minghua
M
Zhu
Yan
Y
Liu
Surapong
S
Koonpaew
Olivia
O
Granillo
Weiguo
W
Zhang
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; C471359:LAB protein, mouse; C419196:LAT2 protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D017455:Receptors, IgE; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium