Nutrient limitations alter cell division control and chromosome segregation through growth-related kinases and phosphatases

In dividing fission yeast Schizosaccharomyces pombe cells, the balance between Wee1 kinase and Cdc25 phosphatase which control the cyclin-dependent kinase (CDK) at the G2–M transition determines the rod-shaped cell length. Under nitrogen source starvation or glucose limitation, however, cell size determination is considerably modulated, and cell size shortening occurs for wild-type cells. For several mutants of kinases or phosphatases, including CDK, target of rapamycin complex (TORC) 1 and 2, stress-responsive mitogen-activated protein kinase (MAPK) Sty1/Spc1, MAPK kinase Wis1, calcium- and calmodulin-dependent protein kinase kinase-like Ssp1, and type 2A and 2A-related phosphatases inhibitor Sds23, this cell shortening does not normally occur. In tor1 and ssp1 mutants, cell elongation is observed. Sds23 that binds to and inhibits 2A and 2A-related phosphatases is synergistic with Ssp1 in the cell size determination and survival under low glucose and nitrogen source. Tor2 (TORC1) is required for growth, whereas Tor1 (TORC2) is needed for determining division size according to different nutrient conditions. Surprisingly, in growth-diminished tor2 mutant or rapamycin-treated cells, the requirement of separase/Cut1-securin/Cut2 essential for chromosome segregation is greatly alleviated. By contrast, defects of tor1 with secruin/ cut2 or overproduction of Cut1 are additive. While Tor1 and Tor2 are opposite in their apparent functions, both may actually coordinate cell division with growth in response to the changes in nutrients.

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Taming platelets with cyclic nucleotides11Abbreviations: ABP, actin binding protein; AC, adenylyl cyclase; cAMP, cyclic AMP; cAMP-PK, cAMP-dependent protein kinase; cGMP, cyclic GMP; cGMP-PK, cGMP-dependent protein kinase; DAG, 1,2-diacylglycerol; EDRF, endothelium-derived relaxing factor; GC, guanylyl cyclase; GP, glycoprotein; Hsp27, heat shock protein 27; IP3, inositol 1,4,5- trisphosphate; IRAG, IP3 receptor-associated cGMP-PK substrate; MAPK, mitogen-activated protein kinase; MAPKAPK-2, MAPK-activated protein kinase-2; MARCKS, myristoylated alanine-rich C kinase substrate; MLC, myosin light chain; MLCK, myosin light chain kinase; PDE, phosphodiesterase; PG-E1, prostaglandin E1; PG-I2, prostacyclin; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; TxA2, thromboxane A2, and VASP, vasodilator-stimulated phosphoprotein.

Biochemical Pharmacology ◽

10.1016/s0006-2952(01)00760-2 ◽

2001 ◽

Vol 62 (9) ◽

pp. 1153-1161 ◽

Cited By ~ 230

Author(s):

Ulrike R. Schwarz ◽

Ulrich Walter ◽

Martin Eigenthaler

Keyword(s):

Protein Kinase ◽

Light Chain ◽

Myosin Light Chain ◽

Mitogen Activated Protein Kinase ◽

Actin Binding ◽

Ip3 Receptor ◽

Dependent Protein Kinase ◽

Kinase Substrate ◽

Mitogen Activated Protein ◽

Dependent Protein

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3-Phosphoinositide–Dependent Protein Kinase-1 Regulates Proliferation and Survival of Cancer Cells with an Activated Mitogen-Activated Protein Kinase Pathway

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-09-0179 ◽

2010 ◽

Vol 8 (3) ◽

pp. 421-432 ◽

Cited By ~ 28

Author(s):

Zhuomei Lu ◽

Mary Ann Cox-Hipkin ◽

William T. Windsor ◽

Anita Boyapati

Keyword(s):

Protein Kinase ◽

Cancer Cells ◽

Mitogen Activated Protein Kinase ◽

Dependent Protein Kinase ◽

Mitogen Activated Protein ◽

Dependent Protein ◽

Kinase Pathway

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Protein kinase A acts at multiple points to inhibit Xenopus oocyte maturation

Molecular and Cellular Biology ◽

10.1128/mcb.14.7.4419-4426.1994 ◽

1994 ◽

Vol 14 (7) ◽

pp. 4419-4426

Author(s):

W Matten ◽

I Daar ◽

G F Vande Woude

Keyword(s):

Protein Kinase ◽

Xenopus Oocytes ◽

Negative Regulator ◽

Mitogen Activated Protein Kinase ◽

Mobility Shift ◽

Dependent Protein Kinase ◽

Multiple Points ◽

Mitogen Activated Protein ◽

Dependent Protein ◽

Phosphatase Activation

In Xenopus oocytes, initiation of maturation is dependent on reduction of cyclic AMP-dependent protein kinase (PKA) activity and the synthesis of the mos proto-oncogene product. Mos is required during meiosis I for the activation of both maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK). Here we show that injection of the catalytic subunit of PKA (PKAc) prevented progesterone-induced synthesis of endogenous Mos as well as downstream MPF and MAPK activation. However, PKAc did not prevent injected soluble Mos product from activating MAPK. While MAPK is activated during Mos-PKAc coinjection, attendant MPF activation is blocked. Additionally, PKAc caused a potent block in the electrophoretic mobility shift of cdc25 that is associated with phosphatase activation. This inhibition of cdc25 activity was not reversed by progesterone, Mos, or MPF. We conclude that PKAc acts as a negative regulator at several points in meiotic maturation by preventing both Mos translation and MPF activation.

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MerTK signaling in macrophages promotes the synthesis of inflammation resolution mediators by suppressing CaMKII activity

Science Signaling ◽

10.1126/scisignal.aar3721 ◽

2018 ◽

Vol 11 (549) ◽

pp. eaar3721 ◽

Cited By ~ 18

Author(s):

Bishuang Cai ◽

Canan Kasikara ◽

Amanda C. Doran ◽

Rajasekhar Ramakrishnan ◽

Raymond B. Birge ◽

...

Keyword(s):

Protein Kinase ◽

Inflammatory Diseases ◽

Critical Role ◽

Mitogen Activated Protein Kinase ◽

Gene Encoding ◽

Endoplasmic Reticulum Calcium ◽

Calcium Calmodulin Dependent ◽

Mitogen Activated Protein ◽

Dependent Protein ◽

Inflammation Resolution

Inflammation resolution counterbalances excessive inflammation and restores tissue homeostasis after injury. Failure of resolution contributes to the pathology of numerous chronic inflammatory diseases. Resolution is mediated by endogenous specialized proresolving mediators (SPMs), which are derived from long-chain fatty acids by lipoxygenase (LOX) enzymes. 5-LOX plays a critical role in the biosynthesis of two classes of SPMs: lipoxins and resolvins. Cytoplasmic localization of the nonphosphorylated form of 5-LOX is essential for SPM biosynthesis, whereas nuclear localization of phosphorylated 5-LOX promotes proinflammatory leukotriene production. We previously showed that MerTK, an efferocytosis receptor on macrophages, promotes SPM biosynthesis by increasing the abundance of nonphosphorylated, cytoplasmic 5-LOX. We now show that activation of MerTK in human macrophages led to ERK-mediated expression of the gene encoding sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2), which decreased the cytosolic Ca2+ concentration and suppressed the activity of calcium/calmodulin-dependent protein kinase II (CaMKII). This, in turn, reduced the activities of the mitogen-activated protein kinase (MAPK) p38 and the kinase MK2, resulting in the increased abundance of the nonphosphorylated, cytoplasmic form of 5-LOX and enhanced SPM biosynthesis. In a zymosan-induced peritonitis model, an inflammatory setting in which macrophage MerTK activation promotes resolution, inhibition of ERK activation delayed resolution, which was characterized by an increased number of neutrophils and decreased amounts of SPMs in tissue exudates. These findings contribute to our understanding of how MerTK signaling induces 5-LOX–derived SPM biosynthesis and suggest a therapeutic strategy to boost inflammation resolution in settings where defective resolution promotes disease progression.

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