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Reference - PMID:23394829 - Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways.

Reference summary

PubMed ID
PMID:23394829
Title
Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways.
Authors
Gupta S, Mana-Capelli S, McLean JR, Chen CT, Ray S, Gould KL, McCollum D
Citation
Curr Biol 2013 Feb 18;23(4):333-8
Publication year
2013
Abstract
The septum initiation network (SIN) regulates multiple functions during late mitosis to ensure successful completion of cytokinesis in Schizosaccharomyces pombe. One mechanism by which the SIN promotes cytokinesis is by inhibiting a competing polarity pathway called the MOR, which is required for initiation of polarized growth following completion of cytokinesis. Mutual antagonism between the two NDR kinase pathways, SIN and MOR, is required to coordinate cytoskeletal rearrangements during the mitosis-interphase transition. To determine how the SIN regulates the MOR pathway, we developed a proteomics approach that allowed us to identify multiple substrates of the SIN effector kinase Sid2, including the MOR pathway components Nak1 kinase and an associated protein, Sog2. We show that Sid2 phosphorylation of Nak1 causes removal of Nak1 from the spindle pole bodies, which may both relieve Nak1 inhibition of the SIN and block MOR signaling by preventing interaction of Nak1 with the scaffold protein Mor2. Because the SIN and MOR are conserved in mammalian cells (Hippo and Ndr1/2 pathways, respectively), this work may provide important insight into how the activities of these essential pathways are coordinated.

Annotation

GO cellular component

GO:0032153 - cell division site

Genes:

GO:0044732 - mitotic spindle pole body

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GO molecular function

GO:0004674 - protein serine/threonine kinase activity

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0002033 - abolished protein phosphorylation during vegetative growth

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Genotypes:

FYPO:0000776 - normal protein phosphorylation during vegetative growth

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Genotypes:

FYPO:0000673 - normal septum assembly

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FYPO:0003250 - premature septum assembly

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Single locus phenotype

FYPO:0000620 - abnormal cell cycle arrest in mitotic metaphase

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FYPO:0002033 - abolished protein phosphorylation during vegetative growth

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FYPO:0000705 - abolished protein-protein interaction

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FYPO:0001837 - increased duration of protein localization to mitotic spindle pole body

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Genotypes:

FYPO:0002482 - inviable spheroid vegetative cell

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Genotypes:

FYPO:0002380 - viable spheroid vegetative cell

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Genotypes:

FYPO:0002104 - viable vegetative cell with normal cell shape

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