Quantitative Phosphoproteomics Reveals Pathways for Coordination of Cell Growth and Division by the Conserved Fission Yeast Kinase Pom1*

Kettenbach, Arminja N.; Deng, Lin; Wu, Youjun; Baldissard, Suzanne; Adamo, Mark E.; Gerber, Scott A.; Moseley, James B.

doi:10.1074/mcp.m114.045245

Cited by 90 publications

(126 citation statements)

References 59 publications

(40 reference statements)

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“…For example, how do Pom1 and other tip factors inhibit cytokinetic machinery, and what is the precise mechanism that positions cytokinetic precursors? The work predicts that Pom1 phosphorylates Cdc15 and potentially other cytokinesis factors, consistent with recently identified Pom1 substrates in S. pombe [16]. Moreover, previous work has shown that S. pombe Cdc15 is part of a pathway that prevents cytokinesis at cell tips through polarity factors such as Pom1 [17].…”

supporting

confidence: 85%

Cytokinesis: Does Mid1 Have an Identity Crisis?

Moseley

2015

Current Biology

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supporting

confidence: 85%

Cytokinesis: Does Mid1 Have an Identity Crisis?

Moseley

2015

Current Biology

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“…Our recent phosphoproteomics study revealed in vivo phosphorylation of Ssp2 (29), the catalytic ␣ subunit of the fission yeast AMPK heterotrimer (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

Phosphatases Generate Signal Specificity Downstream of Ssp1 Kinase in Fission Yeast

Deng

Lee

Schutt

et al. 2017

Molecular and Cellular Biology

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AMPK-related protein kinases (ARKs) coordinate cell growth, proliferation, and migration with environmental status. It is unclear how specific ARKs are activated at specific times. In the fission yeast Schizosaccharomyces pombe, the CaMKKlike protein kinase Ssp1 promotes cell cycle progression by activating the ARK Cdr2 according to cell growth signals. Here, we demonstrate that Ssp1 activates a second ARK, Ssp2/AMPK␣, for cell proliferation in low environmental glucose. Ssp1 activates these two related targets by the same biochemical mechanism: direct phosphorylation of a conserved residue in the activation loop (Cdr2-T166 and Ssp2-T189). Despite a shared upstream kinase and similar phosphorylation sites, Cdr2 and Ssp2 have distinct regulatory input cues and distinct functional outputs. We investigated this specificity and found that distinct protein phosphatases counteract Ssp1 activity toward its different substrates. We identified the PP6 family phosphatase Ppe1 as the primary phosphatase for Ssp2-T189 dephosphorylation. The phosphatase inhibitor Sds23 acts upstream of PP6 to regulate Ssp2-T189 phosphorylation in a manner that depends on energy but not on the intact AMPK heterotrimer. In contrast, Cdr2-T166 phosphorylation is regulated by protein phosphatase 2A but not by the Sds23-PP6 pathway. Thus, our study provides a phosphatase-driven mechanism to induce specific physiological responses downstream of a master protein kinase.KEYWORDS AMPK, Cdr2, Ssp1, fission yeast, kinase, phosphatase, pombe C ells control proliferation, polarized growth, and migration according to nutrient and environmental status. These processes must be tightly regulated during normal growth and development, and loss of this coordination is coupled with distinct steps in the initiation and maturation of tumors (1, 2). The AMP-activated protein kinase (AMPK)-related kinase (ARK) subfamily of protein kinases is essential for coordination of cell growth, proliferation, and migration with environmental status (3). Human cells express at least 13 members of this conserved kinase subfamily, including the metabolic sensor AMPK, the cytoskeletal kinase MARK1/Par-1, and the SAD kinases that regulate cell growth and polarity (4). Given their functions in diverse cell biological processes, it is remarkable that all ARKs can be activated by a shared upstream activating kinase, which phosphorylates the activation loop of ARK kinase domains to turn them "on" (4). To meet the needs of a rapidly changing environment, different ARKs need to be turned on and off at different times. This leads to a simple question: how does a common activation mechanism activate different ARKs at different times?The defining member of the ARK subfamily is AMPK. This conserved heterotrimeric complex is activated by low cellular energy status, typically the result of low levels of environmental nutrients (5). AMPK activation shifts cells toward catabolism and promotes the Warburg effect in cancer cells (5-7). The AMPK heterotrimer consists of a catalytic ␣ subun...

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“…Interestingly, Pom1 also controls Cdc15 localization during mitosis in a Mid1-independent manner, and thus, defines the cortical area for actomyosin ring assembly [21 ]. Of note, Cdc15 was identified as a Pom1 substrate in phosphoproteomics studies in S. pombe [72 ] and given that Cdc15 localization is extensively regulated by Pom1 in S. japonicus, it is likely that this functional interaction is evolutionarily conserved. Interestingly, while the lack of Pom1 leads to Cdc15 relocalization to the growing tip in S. pombe, the opposite is true for S. japonicus where Pom1 deficiency drives Cdc15 accumulation at the non-growing cell tip [21 ].…”

Section: Evolution Of Anillins In the Fission Yeast Cladementioning

confidence: 97%

Comparative biology of cell division in the fission yeast clade

Oliferenko

2015

Current Opinion in Microbiology

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Cytokinesis must be regulated in time and space in order to preserve genome integrity during cell proliferation and to allow daughter cells to adopt distinct fates and geometries during differentiation. The fission yeast Schizosaccharomyces pombe has been a popular model organism for understanding spatiotemporal regulation of cytokinesis in a symmetrically dividing cell. Recent work on another member of the same genus, Schisozaccharomyces japonicus, suggests that S. pombe may have evolved an unusual division site placement mechanism based on a recently duplicated anillin paralog. Here we discuss an extraordinary evolutionary plasticity of cytokinesis within the fission yeast clade and argue that the comparative cell biology approach may provide functional insights beyond those afforded by scrutinizing individual model species.

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Quantitative Phosphoproteomics Reveals Pathways for Coordination of Cell Growth and Division by the Conserved Fission Yeast Kinase Pom1*

Cited by 90 publications

References 59 publications

Cytokinesis: Does Mid1 Have an Identity Crisis?

Cytokinesis: Does Mid1 Have an Identity Crisis?

Phosphatases Generate Signal Specificity Downstream of Ssp1 Kinase in Fission Yeast

Comparative biology of cell division in the fission yeast clade

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