title: Suppression of cell spreading by v-Crk requires Ras-MEK-MAP kinase signaling.
abstract: We investigated the attachment and spreading of v-Crk-transformed cells, v-Crk3Y1, on fibronectin. Transformation by v-Crk virtually suppressed the spreading, but not the attachment, of cells on fibronectin. This suppression of cell spreading was not correlated with the suppression of integrin alpha5 and beta1 expression. However, the spreading of v-Crk3Y1 on fibronectin was dramatically restored by either expression of dominant-negative Ras or treatment with manumycin A, a Ras farnesyltransferase inhibitor. Moreover, both expression of dominant-negative MEK1 and treatment of cells with U0126, a MEK1 inhibitor, restored the cell spreading of v-Crk3Y1. In contrast, neither treatment with LY294002, a PI3K inhibitor, nor expression of dominant-negative C3G showed no effect on cell spreading on fibronectin. Taken together, our results suggest that, among multiple signaling pathways activated by v-Crk, the Ras-MEK1-MAP kinase cascade plays a pivotal role in the suppression of cell spreading on fibronectin, but C3G and the PI3 kinase do not.
authors.affiliation: Department of Molecular Pathogenesis, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraiwa
authors.forename: E
authors.initials: E
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Kurata
authors.forename: A A
authors.initials: AA
authors.lastname: Thant
authors.forename: S
authors.initials: S
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line / Q000166:cytology / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000502:physiology; D048369:MAP Kinase Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D050736:Oncogene Protein v-crk; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017469:Receptors, Fibronectin / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D005353:Fibronectins; D020735:Guanine Nucleotide-Releasing Factor 2; D009025:Morpholines; D009570:Nitriles; D050736:Oncogene Protein v-crk; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D017469:Receptors, Fibronectin; D015682:Retroviridae Proteins, Oncogenic; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017346:Protein Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins; C054474:manumycin