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Protein kinase B phosphorylates AHNAK and regulates its subcellular localization.

Sussman J, Stokoe D, Ossina N, Shtivelman E - J. Cell Biol. (2001)

Bottom Line: We show that AHNAK is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo.Nuclear exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process that also plays a major role in determining extranuclear localization of AHNAK.AHNAK is a new PKB substrate whose function, though unknown, is likely to be regulated by its localization, which is in turn regulated by PKB.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA.

ABSTRACT
AHNAK is a ubiquitously expressed giant phosphoprotein that was initially identified as a gene product subject to transcriptional repression in neuroblastoma. AHNAK is predominantly nuclear in cells of nonepithelial origin, but is cytoplasmic or associated with plasma membrane in epithelial cells. In this study we show that the extranuclear localization of AHNAK in epithelial cells depends on the formation of cell-cell contacts. We show that AHNAK is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo. Nuclear exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process that also plays a major role in determining extranuclear localization of AHNAK. AHNAK is a new PKB substrate whose function, though unknown, is likely to be regulated by its localization, which is in turn regulated by PKB.

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Localization of endogenous AHNAK in HeLa and MDCK cells treated with LMB. Dense cultures either untreated or treated with LMB at 20 ng/ml for 5 h were stained for endogenous AHNAK with a polyclonal anti-AHNAK antiserum against the repeated domain.
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fig8: Localization of endogenous AHNAK in HeLa and MDCK cells treated with LMB. Dense cultures either untreated or treated with LMB at 20 ng/ml for 5 h were stained for endogenous AHNAK with a polyclonal anti-AHNAK antiserum against the repeated domain.

Mentions: To examine whether endogenous AHNAK is also subject to CRM1-mediated nuclear export we have examined the localization of AHNAK in dense HeLa and MDCK cells treated with LMB. Treatment of densely growing HeLa cells with LMB resulted in nuclear redistribution of endogenous AHNAK from a predominantly cytoplasmic localization (Fig. 8) . Similarly, treatment of dense MDCK cells with LMB resulted in the disappearance of the membrane-associated AHNAK and its nuclear translocation in majority of cells.


Protein kinase B phosphorylates AHNAK and regulates its subcellular localization.

Sussman J, Stokoe D, Ossina N, Shtivelman E - J. Cell Biol. (2001)

Localization of endogenous AHNAK in HeLa and MDCK cells treated with LMB. Dense cultures either untreated or treated with LMB at 20 ng/ml for 5 h were stained for endogenous AHNAK with a polyclonal anti-AHNAK antiserum against the repeated domain.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196192&req=5

fig8: Localization of endogenous AHNAK in HeLa and MDCK cells treated with LMB. Dense cultures either untreated or treated with LMB at 20 ng/ml for 5 h were stained for endogenous AHNAK with a polyclonal anti-AHNAK antiserum against the repeated domain.
Mentions: To examine whether endogenous AHNAK is also subject to CRM1-mediated nuclear export we have examined the localization of AHNAK in dense HeLa and MDCK cells treated with LMB. Treatment of densely growing HeLa cells with LMB resulted in nuclear redistribution of endogenous AHNAK from a predominantly cytoplasmic localization (Fig. 8) . Similarly, treatment of dense MDCK cells with LMB resulted in the disappearance of the membrane-associated AHNAK and its nuclear translocation in majority of cells.

Bottom Line: We show that AHNAK is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo.Nuclear exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process that also plays a major role in determining extranuclear localization of AHNAK.AHNAK is a new PKB substrate whose function, though unknown, is likely to be regulated by its localization, which is in turn regulated by PKB.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA.

ABSTRACT
AHNAK is a ubiquitously expressed giant phosphoprotein that was initially identified as a gene product subject to transcriptional repression in neuroblastoma. AHNAK is predominantly nuclear in cells of nonepithelial origin, but is cytoplasmic or associated with plasma membrane in epithelial cells. In this study we show that the extranuclear localization of AHNAK in epithelial cells depends on the formation of cell-cell contacts. We show that AHNAK is a phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo. Nuclear exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process that also plays a major role in determining extranuclear localization of AHNAK. AHNAK is a new PKB substrate whose function, though unknown, is likely to be regulated by its localization, which is in turn regulated by PKB.

Show MeSH
Related in: MedlinePlus