Abstracts (complete list) - Wissenschaft Online

Kerstin Schilling, Bin Hu, Karine Missy, Klaus-Dieter Fischer
Pix proteins in B cell Signalling
alphaPIX is a multi-domain signaling protein with a RhoGEF domain that activates Rac
and CDC42. AlphaPix associates with proteins involved in cytoskeletal-membrane
complexes and cell migration. It has been shown that PIX proteins play roles in some
immune cells, including neutrophils and T cells. We have generated alphaPIX knockout
mice and analyzed their immune system. alphaPIX protein was specifically expressed in
immune cells, unlike its homolog betaPIX, which was expressed in immune cells and in
a wide range of other cells. Although mice lacking alphaPIX had reduced numbers of
mature lymphocytes and defective immune responses, the number of marginal zone B
cells was inceased. In addition, basal migration of B cells and other lymphocytes was
enhanced. Antigen receptor-directed proliferation of alphaPIX - T and B cells was also
reduced, were as LPS induced proliferation of B cells was normal, suggesting for the
first time that alphaPIX is important for B cell receptor (BCR) signaling. In addition,
alphaPIX - B cells showed multiple molecular defects, including increased overall
tyrosine phosphorylation and activation of ERK kinase, and reduced phosphorylation of
PAK kinase following antigen receptor stimulation. These results reveal specific roles for
alphaPIX in the immune system and suggest that alphaPIX is an important signaling
intermediate downstream of the B cell receptor.