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 CXCL12 stimulation. Motility of mutant BAF3 containing DN-Syk increased independent of CXCL12 stimulation. As beta1 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 beta1 integrin.
Matsusaka
Satoshi
S
Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Tohyama
Yumi
Y
He
Jinsong
J
Shi
Yuhong
Y
Hazama
Ryoichi
R
Kadono
Tomomi
T
Kurihara
Rina
R
Tohyama
Kaoru
K
Yamamura
Hirohei
H
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000072377:Syk Kinase
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D004792:Enzyme Precursors; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse