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Homeodomain-interacting protein kinase regulates Hippo pathway-dependent tissue growth.

Current biology : CB (2012-07-31)
Carole L C Poon, Xiaomeng Zhang, Jane I Lin, Samuel A Manning, Kieran F Harvey
ABSTRACT

The Salvador-Warts-Hippo (SWH) pathway is an evolutionarily conserved regulator of tissue growth that is deregulated in human cancer. Upstream SWH pathway components convey signals from neighboring cells via a core kinase cassette to the transcription coactivator Yorkie (Yki). Yki controls tissue growth by modulating activity of transcription factors including Scalloped (Sd). To date, five SWH pathway kinases have been identified, but large-scale phosphoproteome studies suggest that unidentified SWH pathway kinases exist. To identify such kinases, we performed an RNA interference screen and isolated homeodomain-interacting protein kinase (Hipk). Unlike previously identified SWH pathway kinases, Hipk is unique in its ability to promote, rather than repress, Yki activity and does so in parallel to the Yki-repressive kinase, Warts (Wts). Hipk is required for basal Yki activity and is likely to regulate Yki function by promoting its accumulation in the nucleus. Like many SWH pathway proteins, Hipk's function is evolutionarily conserved as its closest human homolog, HIPK2, promotes activity of the Yki ortholog YAP in a kinase-dependent fashion. Further, HIPK2 promotes YAP abundance, suggesting that the mechanism by which HIPK2 regulates YAP has diverged in mammals.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protein Kinase A from bovine heart, ≥0.4 units/μg protein, lyophilized powder
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Protein Kinase Cζ isozyme human, ≥75% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous solution
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Protein kinase CβII isozyme human, >85% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution
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Protein Kinase Cδ isozyme human, >95% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution
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Protein kinase Cγ isozyme human, >95% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution
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Protein Kinase CβI isozyme human, ≥95% (SDS-PAGE), recombinant, expressed in baculovirus infected insect cells, buffered aqueous glycerol solution