Cytoskeletal activation of a checkpoint kinase.
The assembly of cytoskeletal structures is coupled to other cellular processes. We have studied the molecular mechanism by which assembly of the yeast septin cytoskeleton is monitored and coordinated with cell cycle progression by analyzing a key regulatory protein kinase, Hsl1, that becomes activated only when the septin cytoskeleton is properly assembled. We first identified a regulatory region of Hsl1 that physically associates with the kinase domain and found that it performs an autoinhibitory function both in vivo and in vitro. Several septin binding domains lie near and overlap the inhibitory domain; these are important for Hsl1 function, and binding of two septins, Cdc11 and Cdc12, relieves the autoinhibition imposed by the kinase inhibitory domain in vitro. Our results suggest that binding to multiple septins activates Hsl1 kinase activity, thereby promoting cell cycle progression. The high conservation of Hsl1 indicates that similar mechanisms may monitor cytoskeletal organization in other eukaryotes.
Hanrahan
Jessie
J
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Snyder
Michael
M
D001665:Binding Sites / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000201:enzymology*; D005057:Eukaryotic Cells / Q000201:enzymology*; D025461:Feedback, Physiological / Q000502:physiology; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015003:Yeasts
C099502:CDC11 protein, S cerevisiae; C099504:CDC12 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; D010770:Phosphotransferases; D011494:Protein Kinases; C106494:HSL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases