Protein-tyrosine kinase, Syk, is required for CXCL12-induced polarization of B cells

Cell polarization and migration in response to CXCL12 is essential for hematopoiesis. To investigate the role of Syk in CXCL12/ CXCR4-induced signaling, wild-type Syk or its dominant-negative form (DN-Syk) was introduced in mouse pro-B cells, BAF3. With CXCL12 stimulation, BAF3 cells became polarized with the formation of a leading edge and contractile uropod at the rear end with increased motility. Overexpression of wild-type Syk caused enhanced polarization, whereas DN-Syk inhibited cell polarity due to the loss of contractile structure at the rear end, and the altered phenotype was enhanced after CXCL 12 stimulation. Motility of mutant BAF3 containing DN-Syk increased independent of CXCL12 stimulation. As PI integrin-mediated cell adhesion was inhibited, decreased adhesion might promote motility. CXCL12 stimulation led to prompt activation of RhoA, but expression of DN-Syk suppressed RhoA activation. These results demonstrate that Syk participates in CXCL I 2-induced cell polarization, which occurs in concert with cell adhesion mediated by beta1 integrin. (C) 2005 Elsevier Inc. All rights reserved.