The kinase knows

杨柳

Snyder/Elsevier! U2 C1 `) ~: x

' c: x6 Z. i6 l% ~# O  y' _2 i$ l8 U4 f% k$ ^CFells monitor the assembly of cytoskeletal structures via direct binding and activation of a checkpoint kinase, as shown by Jessie Hanrahan and Michael Snyder (Yale University, New Haven, CT).
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5 Q3 H7 t$ t8 u- jCytoskeletal reorganization is needed during various events in the cell cycle. In budding yeast, for example, a ring of septin filaments separates the mother cell from the forming bud. The ring must be completed before the cell can enter mitosis. This landmark is signaled by the Hsl1 kinase, which is activated upon ring assembly. Snyder wondered, "how do  recognize when a macromolecular complex like the cytoskeleton is assembled? The thought seems daunting at first." But he found a relatively simple answer for Hsl1〞it is either bound to the septin ring or is in an inactive conformation.
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9 b9 A$ r. H0 J% X; DThe authors identified a site in the large noncatalytic portion of Hsl1 that binds to and inactivates the kinase domain. This autoinhibitory domain overlaps with three sites that bind to two different septin subunits. In vitro, septins activate the kinase by displacing the inhibitory domain. In vivo, the septins have to be polymerized, as previous results showed that unassembled subunits do not activate Hsl1. This may be due to the spacing of the septin binding sites and the need for all three sites to be filled to displace the inhibitory domain.
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This sensing mechanim may extend to other cytoskeletal structures. Microtubules, for instance, are bound by a relative of Hsl1 called MARK. Says Snyder, " is attractive as a universal mechanism to monitor assembly of cytoskeletons specifically, and maybe macromolecular complexes in general."% g/ u- \6 E& t1 r+ W
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. D/ L' b; A: J: _Hanrahan, J., et al. 2003. Mol. Cell. 12:663–673.(Hsl1 (red), is activated at the bud neck)