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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: 3T3 Cells, Animals, COS Cells, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle Proteins, GTP Phosphohydrolases, GTP-Binding Proteins, Gene Expression Regulation, Guanine Nucleotide Exchange Factors, Humans, JNK Mitogen-Activated Protein Kinases, Mice, Mitogen-Activated Protein Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, cdc42 GTP-Binding Protein.
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Are faciogenital dysplasia protein ( FGD1 ) and Vav , two related proteins required for normal embryonic development , upstream regulators of Rho GTPases? Context: Dbl, a guanine nucleotide exchange factor (GEF) for members of the Rho family of small GTPases, is the prototype of a family of 15 related proteins. The majority of proteins that contain a DH (Dbl homology) domain were isolated as oncogenes in transfection assays, but two members of the DH family, FGD1 (the product of the faciogenital dysplasia or Aarskog-Scott syndrome locus) and Vav, have been shown to be essential for normal embryonic development. Mutations to the FGD1 gene result in a human developmental disorder affecting specific skeletal structures, including elements of the face, cervical vertebrae and distal extremities. Homozygous Vav-/- knockout mice embryos are not viable past the blastocyst stage, indicating an essential role of Vav in embryonic implantation. Here, we show that the microinjection of FGD1 and Vav into Swiss 3T3 fibroblasts induces the polymerization of actin and the assembly of clustered integrin complexes. FGD1 activates Cdc42, whereas Vav activates Rho, Rac and Cdc42. In addition, FGD1 and Vav stimulate the mitogen activated protein kinase cascade that leads to activation of the c-Jun kinase SAPK/JNK1.
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We conclude that FGD1 and Vav are regulators of the Rho GTPase family. Along with their target proteins Cdc42, Rac and Rho, FGD1 and Vav control essential signals required during embryonic development. Final Decision: yes