Early effects of pp60(v-src) kinase activation on caveolae.
Members of the nonreceptor tyrosine kinase family appear to be targeted to caveolae membrane. We have used a Rat-1 cell expressing a temperature sensitive pp60(v-src) kinase to assess the initial changes that take place in caveolae after kinase activation. Within 24-48 h after cells were shifted to the permissive temperature, a set of caveolae-specific proteins became phosphorylated on tyrosine. During this period there was a decline in the caveolae marker protein, caveolin-1, a loss of invaginated caveolae, and a 70% decline in the sphingomyelin content of the cell. One of the phosphorylated proteins was caveolin-1 but it was associated in coimmunoprecipitation assays with both a 30 kDa and a 27 kDa tyrosine-phosphorylated protein. Finally, the cells changed from having a typical fibroblast morphology to a rounded shape lacking polarity. In light of the recent evidence that diverse signaling events originate from caveolae, pp60(v-src) kinase appears to cause global changes to this membrane domain that might directly contribute to the transformed phenotype.
Ko
Y G
YG
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235-9039, USA.
Liu
P
P
Pathak
R K
RK
Craig
L C
LC
Anderson
R G
RG
D000818:Animals; D016227:Benzoquinones; D051242:Caveolin 1; D022461:Caveolins; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004789:Enzyme Activation; D005347:Fibroblasts; D047029:Lactams, Macrocyclic; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D015388:Organelles / Q000201:enzymology*; D019000:Phosphotyrosine / Q000276:immunology / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D012260:Ribonucleases / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
D016227:Benzoquinones; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D002518:Ceramides; D047029:Lactams, Macrocyclic; D008055:Lipids; D008565:Membrane Proteins; D011809:Quinones; D013109:Sphingomyelins; D017828:Rifabutin; D019000:Phosphotyrosine; C020754:herbimycin; D015688:Oncogene Protein pp60(v-src); D012260:Ribonucleases