Cloning of MASK, a novel member of the mammalian germinal center kinase III subfamily, with apoptosis-inducing properties.
We have cloned a novel human GCK family kinase that has been designated as MASK (Mst3 and SOK1-related kinase). MASK is widely expressed and encodes a protein of 416 amino acid residues, with an N-terminal kinase domain and a unique C-terminal region. Like other GCK-III subfamily kinases, MASK does not activate any mitogen-activated protein kinase pathways. Wild type MASK, but not a form lacking the C terminus, exhibits homophilic binding in the yeast two-hybrid system and in coimmunoprecipitation experiments. Additionally, deletion of this C-terminal region of MASK leads to an increased kinase activity toward itself as well as toward an exogenous substrate, myelin basic protein. A potential caspase 3 cleavage site (DESDS) is present in the C-terminal region of MASK, and we show that MASK is cleaved in vitro by caspase 3. Finally, wild type and C-terminally truncated forms of MASK can both induce apoptosis upon overexpression in mammalian cells that is abrogated by CrmA, suggesting involvement of MASK in the apoptotic machinery in mammalian cells.
Dan
Ippeita
I
Kusumi Membrane Organizer Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, 5-11-33 Chiyoda, Nagoya 460-0012, Japan.
Ong
Shao-En
SE
Watanabe
Norinobu M
NM
Blagoev
Blagoy
B
Nielsen
Mogens M
MM
Kajikawa
Eriko
E
Kristiansen
Troels Z
TZ
Mann
Matthias
M
Pandey
Akhilesh
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D003001:Cloning, Molecular; D053938:DNA Fragmentation; D017931:DNA Primers; D005091:Exons; D018858:Germinal Center / Q000201:enzymology; D000081410:Germinal Center Kinases; D006801:Humans; D007438:Introns; D008322:Mammals; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D000099317:Hippo Kinases
D017931:DNA Primers; D000081410:Germinal Center Kinases; D010446:Peptide Fragments; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C430908:STK26 protein, human; D000099317:Hippo Kinases