Microtubule-associated protein tau in human prostate cancer cells: isoforms, phosphorylation, and interactions.
Tau is a microtubule-associated protein whose function has been investigated primarily in neurons. Recently, tau expression has been correlated with increased drug resistance in various cancers of non-neuronal tissues. In this report, we investigate the tau expressed in cancerous prostate lines ALVA-31, DU 145, and PC-3. Prostate cancer tau is heat-stable and highly phosphorylated, containing many of the modifications identified in Alzheimer's disease brain tau. RT-PCR and phosphatase treatment indicated that all six alternatively spliced adult brain tau isoforms are expressed in ALVA-31 cells, and isoforms containing exon 6 as well as high molecular weight tau isoforms containing either exon 4A or a larger splice variant of exon 4A are also present. Consistent with its hyperphosphorylated state, a large proportion of ALVA-31 tau does not bind to microtubules, as detected by confocal microscopy and biochemical tests. Finally, endogenous ALVA-31 tau can interact with the p85 subunit of phosphatidylinositol 3-kinase, as demonstrated by co-immunoprecipitations and in vitro protein-binding assays. Our results suggest that tau in prostate cancer cells does not resemble that from normal adult brain and support the hypothesis that tau is a multifunctional protein.
Souter
Skye
S
Program in Molecular and Cellular Biology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Lee
Gloria
G
D000328:Adult; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008297:Male; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D016875:tau Proteins / Q000378:metabolism*
D020033:Protein Isoforms; D016875:tau Proteins; D019869:Phosphatidylinositol 3-Kinases
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