Journal of Cell Science 116, e702-e702 (2003)
Copyright © 2003 The Company of Biologists Limited
Multi-tasking with GSK3
Initially shown to phosphorylate glycogen synthase, GSK3 is a
multifunctional kinase that regulates numerous cellular processes. Unlike many
kinases, it is generally active in cells and inhibited by signalling;
moreover, it tends to favour substrates that have already been phosphorylated
(`primed') by other kinases. In a Commentary on
p. 1175, Bradley Noble and
James Woodgett review recent advances in our understanding of the structure
and functions of GSK3. The solving of its crystal structure, for example, has
revealed where the priming phosphate group on the substrate binds and
indicates that this optimizes orientation of the kinase domain and positions
the substrate correctly in the catalytic groove. Other studies have shown that
the major transducers in Wnt and Hedgehog signalling — ß-catenin
and Cubitus interruptus — are GSK3 targets and primed by casein kinase I
and protein kinase A. Given the abnormal GSK3 activity associated with
conditions such as Alzheimer's and diabetes, the development of several small
molecule inhibitors of GSK3 is also exciting — although Noble and
Woodgett note that their therapeutic benefits might be limited given the
pleiotropic nature of the kinase.
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Related articles in JCS:
- GSK-3: tricks of the trade for a multi-tasking kinase
- Bradley W. Doble and James R. Woodgett
JCS 2003 116: 1175-1186.
[Abstract]
[Full Text]
