Functional role of focal adhesion kinase in the process of implantation.
The expression and function of focal adhesion kinase (FAK) in human decidual cells were investigated. This kinase is localized to focal adhesions in fibroblasts, and is phosphorylated on tyrosine in normal and src-transformed fibroblasts. Immunofluorescent staining revealed that the cultured decidual cells expressed high levels of FAK at the cell periphery. Double stainings for FAK and phosphotyrosine, FAK and talin, and FAK and beta1 integrin demonstrated that FAK co-localized with integrins in cellular focal adhesions. Mouse blastocysts became attached to cultured decidual cells after embryos hatched from the zona pellucida. The majority of hatched blastocysts attached to human decidual cells within 24 h of culture. Blastocysts attached to decidual cells exhibited extensive outgrowth after 48 h. Treatment of decidual cells with herbimycin A, a tyrosine kinase inhibitor, did not affect the rate of hatching or attachment of blastocysts. However, the outgrowth of embryos on the decidual cells was inhibited by the addition of herbimycin A in a dose-dependent manner, implying that blastocyst attachment and outgrowth are mediated by different mechanisms. This study suggests that tyrosine phosphorylation of FAK on decidual cells may be important in development and differentiation following attachment.
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
S
S
Shiokawa
Y
Y
Yoshimura
S
S
Nagamatsu
H
H
Sawa
H
H
Hanashi
K
K
Sakai
K
K
Noguchi
Y
Y
Nakamura
D000328:Adult; D000818:Animals; D016227:Benzoquinones; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000201:enzymology; D010064:Embryo Implantation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D047029:Lactams, Macrocyclic; D051379:Mice; D008813:Mice, Inbred ICR; D019000:Phosphotyrosine / Q000378:metabolism; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D016608:Talin / Q000378:metabolism
D016227:Benzoquinones; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D019012:Integrin beta1; D047029:Lactams, Macrocyclic; D011809:Quinones; D016608:Talin; D017828:Rifabutin; D019000:Phosphotyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse