Signaling molecules that mediate the actions of FGF.
Signaling by fibroblast growth factor (FGF) is critical for cellular growth and differentiation. We have studied the role of FGF and its receptor in development and also the signaling pathways utilized by these molecules. Transgenic mice expressing a dominant negative FGF receptor specifically in lung tissue fail to develop lungs. These findings suggest that FGF signaling is important for airway branching and alveolar formation. In Xenopus embryos, FGF is involved in the development of posterior structures. Induction of mesoderm by FGF is mediated by the serine-threonine kinase RAF. The expression of a dominant negative RAF selectively blocks the mesoderm-inducing action of FGF. Expression of activated RAF accentuated the development of posterior structures Other intracellular molecules that are involved with FGF signaling include RAS, a low-molecular weight GTP-binding protein. We have identified a novel gene (RIP, for RAS-interacting protein) that contains a RAS-binding domain. This domain is found in at least one other protein, ralGDS. Both RIP and ralGDS bind to activated RAS suggesting that these proteins are likely candidates for mediators of RAS function. These findings help elucidate the role of FGF signaling in development.
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Department of Medicine, University of California, San Francisco 94143-0130, USA.
Kikuchi
A
A
Peters
K G
KG
MacNicol
A M
AM
Muslin
A J
AJ
Williams
L T
LT
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000737:chemistry; D006160:Guanosine Triphosphate / Q000502:physiology; D008168:Lung / Q000196:embryology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology; D020726:ral Guanine Nucleotide Exchange Factor; D020668:rap GTP-Binding Proteins; D018631:ras Proteins / Q000502:physiology*
D011506:Proteins; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D020726:ral Guanine Nucleotide Exchange Factor; D005346:Fibroblast Growth Factors; D006160:Guanosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins; D018631:ras Proteins