Newest findings on the oldest oncogene; how activated src does it.
Oncogenic forms of the non-receptor tyrosine kinase Src alter cell structure, in particular the actin cytoskeleton and the adhesion networks that control cell migration, and also transmit signals that regulate proliferation and cell survival. Recent work indicates that they do so by influencing the RhoA-ROCK pathway that controls contractile actin filament assembly, the STAT family of transcription factors needed for transformation, and the Cbl ubiquitin ligase that controls Src protein levels. These studies also shed light on the role of focal adhesion kinase (FAK) downstream of v-Src and other signalling pathways in controlling migration, invasion and survival of transformed cells. Src directly phosphorylates integrins and can also modulate R-Ras activity. Moreover, it stimulates the E-cadherin regulator Hakai, interacts with and phosphorylates the novel podosome-linked adaptor protein Fish, and progressively phosphorylates the gap junction component connexion 43. A recurring theme is the identification of novel and important Src substrates that mediate key biological events associated with transformation.
Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. m.frame@beatson.gla.ac.uk
Margaret C
MC
Frame
D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000503:physiopathology; D018031:Connexin 43 / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017629:Gap Junctions / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016391:Genes, src; D006801:Humans; D016023:Integrins / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology; D008954:Models, Biological; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction
D018031:Connexin 43; D016023:Integrins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); C496050:PTK2 protein, human; D020782:Matrix Metalloproteinases