Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK.
FAK is a unique non-receptor protein tyrosine kinase that was found in cellular focal adhesions. An increasing number of in vitro observations has suggested that FAK mediates signaling through integrins brought about by interactions with extracellular matrix (ECM). It is highly tyrosine-phosphorylated in v-src-transformed cells and during embryogenesis. To clarify the function of FAK in cell-ECM interactions, embryonic phenotype of its mutant was analysed. FAK-deficient embryos could implant and initiate gastrulation normally, but showed abnormalities in subsequent development. The abnormalities were characterized as a general deficiency in mesoderm, and the phenotype was quite similar to that caused by fibronectin-deficiency. The results suggest that FAK mediates fibronectin-integrin interactions uniquely at this stage of development, thereby playing an essential role in development of mesodermal cell lineages.
D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005775:Gastrula / Q000201:enzymology / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D019868:Kanamycin Kinase; D008297:Male; D008648:Mesoderm / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains / Q000196:embryology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015815:Cell Adhesion Molecules; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse