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Elm1 kinase activates the spindle position checkpoint kinase Kin4.

Caydasi AK, Kurtulmus B, Orrico MI, Hofmann A, Ibrahim B, Pereira G - J. Cell Biol. (2010)

Bottom Line: How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established.Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4.Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment.

View Article: PubMed Central - HTML - PubMed

Affiliation: German Cancer Research Center, DKFZ-ZMBH Alliance, Molecular Biology of Centrosomes and Cilia, 69120 Heidelberg, Germany.

ABSTRACT
Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4.

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Model depicting the mechanisms by which Elm1 and Rts1 regulate Kin4. Elm1 phosphorylates Kin4 at threonine 209. This step is essential for Kin4 catalytic activity and subsequent hyperphosphorylation, which might require Kin4 kinase activity. Rts1 regulates Kin4 localization to the cortex and SPB (Chan and Amon, 2009; this study) by an unknown mechanism.
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fig10: Model depicting the mechanisms by which Elm1 and Rts1 regulate Kin4. Elm1 phosphorylates Kin4 at threonine 209. This step is essential for Kin4 catalytic activity and subsequent hyperphosphorylation, which might require Kin4 kinase activity. Rts1 regulates Kin4 localization to the cortex and SPB (Chan and Amon, 2009; this study) by an unknown mechanism.

Mentions: Our data strongly support the view that Elm1 directly phosphorylates Kin4 independently of Rts1 function (Fig. 10). Purified Elm1 phosphorylated Kin4 in vitro and deletion of ELM1 abolished Kin4 hyperphosphorylation in the presence or absence of RTS1 in vivo. Interestingly, Kin4 hyperphosphorylation was lost in cells expressing a kinase-dead mutant of KIN4 (Fig. 5). This suggested that Kin4 kinase activity might be required to promote Kin4 hyperphosphorylation either by autophosphorylation or in a positive feedback loop together with Elm1 or other kinases (Fig. 10). So far, we have been unable to detect Kin4 autophosphorylation in vitro. However, we cannot exclude the possibility that Kin4 might be subjected to autophosphorylation events that are dependent on a particular cellular context.


Elm1 kinase activates the spindle position checkpoint kinase Kin4.

Caydasi AK, Kurtulmus B, Orrico MI, Hofmann A, Ibrahim B, Pereira G - J. Cell Biol. (2010)

Model depicting the mechanisms by which Elm1 and Rts1 regulate Kin4. Elm1 phosphorylates Kin4 at threonine 209. This step is essential for Kin4 catalytic activity and subsequent hyperphosphorylation, which might require Kin4 kinase activity. Rts1 regulates Kin4 localization to the cortex and SPB (Chan and Amon, 2009; this study) by an unknown mechanism.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3101594&req=5

fig10: Model depicting the mechanisms by which Elm1 and Rts1 regulate Kin4. Elm1 phosphorylates Kin4 at threonine 209. This step is essential for Kin4 catalytic activity and subsequent hyperphosphorylation, which might require Kin4 kinase activity. Rts1 regulates Kin4 localization to the cortex and SPB (Chan and Amon, 2009; this study) by an unknown mechanism.
Mentions: Our data strongly support the view that Elm1 directly phosphorylates Kin4 independently of Rts1 function (Fig. 10). Purified Elm1 phosphorylated Kin4 in vitro and deletion of ELM1 abolished Kin4 hyperphosphorylation in the presence or absence of RTS1 in vivo. Interestingly, Kin4 hyperphosphorylation was lost in cells expressing a kinase-dead mutant of KIN4 (Fig. 5). This suggested that Kin4 kinase activity might be required to promote Kin4 hyperphosphorylation either by autophosphorylation or in a positive feedback loop together with Elm1 or other kinases (Fig. 10). So far, we have been unable to detect Kin4 autophosphorylation in vitro. However, we cannot exclude the possibility that Kin4 might be subjected to autophosphorylation events that are dependent on a particular cellular context.

Bottom Line: How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established.Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4.Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment.

View Article: PubMed Central - HTML - PubMed

Affiliation: German Cancer Research Center, DKFZ-ZMBH Alliance, Molecular Biology of Centrosomes and Cilia, 69120 Heidelberg, Germany.

ABSTRACT
Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4.

Show MeSH
Related in: MedlinePlus