| Research Abstract |
Drs. Chan and Kurosaki have coworked the molecular mechanisms by which BLNK, an adaptor molecule, participates in BCR signaling pathways. Using reconstitution studies, we found that SLP-76, BLNK-related adaptor molecule expressed in T cells, canhot reconstitute BCR functions in BLNK-deficient DT40 B cells. This could be attributable to inability of SLP-76 to be recruited into glycolipid-enriched microdomains (GEMS) after antigen receptor cross-linking. Supporting this idea, the BCR function can be restored when a membrane-associated SLP-76 chimera is enforcedly localized to GEMS. Moreover, addition of both LAT and Gads to SLP-76 allows SLP-76 to be recruited into GEMs, whereby the BCR function is reconstituted. The Gads function can be replaced by overexpression of Grb2.In contrast to SLP-76.BLNK did not require Grb2 families for its recruitment to GEMs. Hence, these data suggest a functional overlap between BLNK and SLP-76, while emphasizing the difference in requirement for additional adaptor molecules in their targeting to GEMs.
Drs. Clark and Kurosaki coworked the function of Bam32, another adaptor molecule, in BCR signaling. By analyzing Bam32-deficient DT40 B cells, we have provided the evidence that Bam32 is involved in BCR-mediated/calcium pathway, presumably explaining the defective NF-AT and NF-KB activation.
|
