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

• Published in: Biochemical and biophysical research communications Vol. 328; no. 4; pp. 1163 - 1169
• Main Authors: Matsusaka, Satoshi, Tohyama, Yumi, He, Jinsong, Shi, Yuhong, Hazama, Ryoichi, Kadono, Tomomi, Kurihara, Rina, Tohyama, Kaoru, Yamamura, Hirohei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.03.2005
• Subjects: Adhesion; Animals; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cell Polarity - drug effects; Cell Polarity - physiology; Cells, Cultured; Chemokine CXCL12; Chemokines, CXC - pharmacology; CXCL12; CXCR4; Dose-Response Relationship, Drug; Enzyme Precursors - genetics; Enzyme Precursors - metabolism; Hematopoiesis; Hematopoiesis - physiology; Integrin; Integrin beta1 - metabolism; Intracellular Signaling Peptides and Proteins; Mice; Migration; Polarization; Protein-tyrosine kinase; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Recombinant Proteins - metabolism; Syk; Syk Kinase; Polarization; CXCL12; Integrin; Syk; Hematopoiesis; Migration; CXCR4; Protein-tyrosine kinase; Adhesion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.01.076

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 CXCL12 stimulation. Motility of mutant BAF3 containing DN-Syk increased independent of CXCL12 stimulation. As β1 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 CXCL12-induced cell polarization, which occurs in concert with cell adhesion mediated by β1 integrin.