The hCSE1/CAS protein is phosphorylated by HeLa extracts and MEK-1: MEK-1 phosphorylation may modulate the intracellular localization of CAS.
hCSE1/CAS (CAS), the human homologue of the yeast chromosome segregation gene CSE1, is a nuclear transport factor that plays a role in proliferation and apoptosis. A MEK-1 phosphorylation sequence in CAS raises the possibility that MEK-phosphorylation regulates the function of CAS. CAS protein from cell extracts shows covalent charge modifications; one of these charge variants contains phosphotyrosine. CAS protein can be captured from cell extracts by immobilized anti-phosphotyrosine antibodies. We have produced recombinant protein fragments containing the N-terminal or central portion of CAS and found that the N-terminal fragment, which contains a putative MEK phosphorylation site, is phosphorylated by the HeLa extracts and MEK-1. Treatment of cells with an inhibitor of MEK-1 phosphorylation in vivo changes the intracellular localization of CAS from predominantly cytoplasmic to nuclear. This suggests that a function of CAS in nuclear transport may be regulated by phosphorylation.
Division of Basic Sciences, National Cancer Institute, National Institute of Child Health and Development, National Institutes of Health, National Institutes of Health, Bethesda, Maryland, 20892-4255, USA.
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U
Scherf
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P
Kalab
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M
Dasso
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Pastan
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Brinkmann
D017209:Apoptosis; D001692:Biological Transport; D029563:Cellular Apoptosis Susceptibility Protein; D006367:HeLa Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
D029563:Cellular Apoptosis Susceptibility Protein; D011506:Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases