Sci. STKE, 5 December 2000
Immunology B Cell Production and the Missing Lnk
When lnk was cloned, it was hoped that Lnk would turn out to be the long-sought transmembrane adaptor protein essential for T cell signaling now known as LAT. Unfortunately, Lnk could perform most but not all functions ascribed to LAT, and the further characterization of Lnk was not pursued. Now, by generating a lnk knockout mouse, Takaki et al. demonstrate that Lnk controls B cell but not T cell production and maturation. Thymic cellularity and T cell development in lnk-deficient mice were normal, as was calcium influx in Lnk-negative T cells, indicating that Lnk is not essential for T cell development or signaling. However, increased numbers of splenic immature B cells and bone marrow B cell precursors from lnk-/- mice were observed. The capacity of activated Lnk-negative mature B cells to signal was normal, as measured by protein tyrosine phosphorylation and calcium levels, indicating that Lnk is not essential for B cell-receptor signaling. In conditions suitable for colony formation, Lnk-deficient B cell precursors produced more colonies than did Lnk-positive cells, indicating that Lnk normally functions to control B cell production. Lnk was originally identified as a 38-kD protein; however, Takaki et al. showed that full-length Lnk is a 68-kD protein and belongs to a family of adaptor proteins including APS [adaptor molecule containing pleckstrin homology (PH) and Src homology-2 (SH2) domains] and SH2-B. Whether these other adaptor proteins act in redundant fashion to Lnk or have specific functions in other signaling pathways must await further inquiry.
Takaki, S., Sauer, K., Iritani, B.M., Chien, S., Ebihara, Y., Tsuji, K., Takatsu, K., and Perlmutter, R.M. (2000) Control of B cell production by the adaptor protein Lnk: Definition of a conserved family of signal-modulating proteins. Immunity 13: 599-609. [Online Journal]
Citation: B Cell Production and the Missing Lnk. Sci. STKE 2000, tw4 (2000).
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