Role of tyrosine kinase Csk in G protein-coupled receptor- and receptor tyrosine kinase-induced fibroblast cell migration.
Tyrosine kinase Csk is essential for mouse embryonic development. Csk knock-out mice died at early stages of embryogenesis (around embryonic day 10). The molecular mechanism for this defect is not completely understood. Here we report that Csk deficiency in mouse embryonic fibroblast cells blocked cell migration induced by lysophosphatidic acid through G protein-coupled receptors, by platelet-derived growth factor and epidermal growth factor through receptor tyrosine kinases, and by serum. Re-expression of Csk in these Csk-deficient cells rescued the migratory phenotype. Furthermore, deletion of Csk did not interfere with Rac activation and lamellipodia formation, but impaired the focal adhesions. Our data demonstrate a critical role for Csk in cell migration.
McGarrigle
Deirdre
D
Department of Physiology, Cornell University Weill Medical College, New York, NY 10021, USA.
Shan
Dandan
D
Yang
Shengyu
S
Huang
Xin-Yun
XY
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D002384:Catalysis; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D013997:Time Factors; D014945:Wound Healing; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
D000199:Actins; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; C032881:lysophosphatidic acid