title: Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways.
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.
authors: Department of Microbiology and Physiological Systems and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Sneha
authors: S
authors: Gupta
authors: Sebastian
authors: S
authors: Mana-Capelli
authors: Janel R
authors: JR
authors: McLean
authors: Chun-Ti
authors: CT
authors: Chen
authors: Samriddha
authors: S
authors: Ray
authors: Kathleen L
authors: KL
authors: Gould
authors: Dannel
authors: D
authors: McCollum
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D048749:Cytokinesis / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D040901:Proteomics; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008840:Microfilament Proteins; C467580:Mor2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C113816:Sid2 protein, S pombe; C500976:Nak1 protein, S pombe; D017346:Protein Serine-Threonine Kinases
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