Subject: Novel kinase: gasket
We predict a novel member of the glycogen synthetase kinase 3 family,
gasket (gskt = glycogen synthetase kinase three) based on genomic sequence
analysis. gskt consists of a single exon, mapping to 100C1-3, which encodes
a protein with clear homology to shaggy/zeste-white 3, and the vertebrate
genes GSK alpha and beta. gskt and sgg are more similar to each other than
either is to GSKa/b, indicating that an ancestral gene duplicated
independently in the fly and vertebrate lineages.
sgg has three known splice forms; one core short form, and longer forms
that extend either the N or C termini. gskt aligns from end to end with the
short form (sgg-P2). The N-terminal kinase domains (75% identical AA
sequence) are followed by a region of ~55% sequence homology, and a
divergent ~140 AA C-terminal tail with ~25% sequence identity. This last
region is not supported by EST sequence and may be mispredicted, as sgg and
human GSK3 share some similarity in this region.
21 ESTs cover this open reading frame and extend 5' to give a 130 nt UTR,
as well as covering from residues 1-337 of the 501 AA open reading frame.
19 ESTs are from the AT (adult testes) library and 2 from the GH (adult
head) library.
Vertebrate GSK3 genes are involved in insulin signalling: phosphorylation
and inactivation of GSK3 by ATK blocks the inhibitory phosphorylation of
GSK3 substrates including glygogen synthetase and eIF2B. sgg has been well
studied in wg signaling, but no role in insulin response has been
described; it may be that gskt has some role in this process, or in
signalling downstream of frizzled receptors other than the fz2 wingless
receptor.
\-Gerard Manning.