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SIK1/SOS2 networks: decoding sodium signals via calcium-responsive protein kinase pathways.

Bertorello AM, Zhu JK - Pflugers Arch. (2009)

Bottom Line: The specific ionic stress (elevated intracellular sodium) is followed by changes in intracellular calcium; the calcium signals are sensed by calcium-binding proteins and lead to activation of SIK1 or SOS2.These kinases target major plasma membrane transporters such as the Na(+),K(+)-ATPase in mammalian cells, and Na(+)/H(+) exchangers in the plasma membrane and membranes of intracellular vacuoles of plant cells.Activation of these networks prevents abnormal increases in intracellular sodium concentration.

View Article: PubMed Central - PubMed

Affiliation: Membrane Signaling Networks, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital-Solna, Stockholm, Sweden. alejandro.bertorello@ki.se

ABSTRACT
Changes in cellular ion levels can modulate distinct signaling networks aimed at correcting major disruptions in ion balances that might otherwise threaten cell growth and development. Salt-inducible kinase 1 (SIK1) and salt overly sensitive 2 (SOS2) are key protein kinases within such networks in mammalian and plant cells, respectively. In animals, SIK1 expression and activity are regulated in response to the salt content of the diet, and in plants SOS2 activity is controlled by the salinity of the soil. The specific ionic stress (elevated intracellular sodium) is followed by changes in intracellular calcium; the calcium signals are sensed by calcium-binding proteins and lead to activation of SIK1 or SOS2. These kinases target major plasma membrane transporters such as the Na(+),K(+)-ATPase in mammalian cells, and Na(+)/H(+) exchangers in the plasma membrane and membranes of intracellular vacuoles of plant cells. Activation of these networks prevents abnormal increases in intracellular sodium concentration.

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Salt sensing in mammalian cells.The SIK1 pathway is depicted with its presently known signaling components. Increases in Na+ permeability (from basal = ~9 to ~14 mM, [56]) promote transient increases in intracellular Ca2+ via the Na+/Ca2+ exchanger. Sequential activation of calmodulin, calmodulin kinase 1 (CaMK1), and salt-inducible kinase 1 (SIK1) leads to phosphorylation of a phosphomethylesterase 1 (PME-1), promoting its dissociation from the protein phosphatase 2A (PP2A), which is then activated. Dephosphorylation of the Na+,K+-ATPase α-subunit (NK-inactive) triggers the increase in its catalytic activity (NK-active)
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Fig4: Salt sensing in mammalian cells.The SIK1 pathway is depicted with its presently known signaling components. Increases in Na+ permeability (from basal = ~9 to ~14 mM, [56]) promote transient increases in intracellular Ca2+ via the Na+/Ca2+ exchanger. Sequential activation of calmodulin, calmodulin kinase 1 (CaMK1), and salt-inducible kinase 1 (SIK1) leads to phosphorylation of a phosphomethylesterase 1 (PME-1), promoting its dissociation from the protein phosphatase 2A (PP2A), which is then activated. Dephosphorylation of the Na+,K+-ATPase α-subunit (NK-inactive) triggers the increase in its catalytic activity (NK-active)

Mentions: The signaling events by which sodium rapidly triggers the activation of SIK1 appear to occur in the proximity of the Na+,K+-ATPase. They are initiated by a parallel influx of calcium (throughout the reverse Na+/Ca2+ exchanger), and are possibly limited to a discrete number of Na+,K+-ATPase units (Fig. 4). A transient rise in intracellular calcium, via the reverse Na+/Ca2+-exchanger, represents the coding signal for the activation of calmodulin kinases (in particular CaMK1) that in turn phosphorylate SIK1 at a threonine residue within its SNH domain (Thr-322). Activated SIK1 does not control Na+,K+-ATPase activity directly through protein phosphorylation (neither the α- nor the β-subunits contain a SIK1 consensus phosphorylation site) but rather by promoting the dephosphorylation of the Na+,K+-ATPase α-subunit. The latter also suggests that dephosphorylation does not result from a direct effect of sodium on Na+,K+-ATPase but rather from a more sophisticated signaling network. The Na+,K+-ATPase constitutively associates with a protein phosphatase 2A (PP2A) [32, 44], and it is logical to think that, if this phosphatase is constantly present in an active form, the Na+,K+-ATPase would never be subjected to phosphorylation, or that this event has to be tightly regulated. Activation of protein phosphatases is not only important for regulating the state of Na+,K+-ATPase subunit phosphorylation [23] but also for regulating the cellular mechanisms responsible for its traffic to and from the plasma membrane [8]. Increases in intracellular sodium result in activation of PP2A, and this effect requires an active SIK1 [44].Fig. 4


SIK1/SOS2 networks: decoding sodium signals via calcium-responsive protein kinase pathways.

Bertorello AM, Zhu JK - Pflugers Arch. (2009)

Salt sensing in mammalian cells.The SIK1 pathway is depicted with its presently known signaling components. Increases in Na+ permeability (from basal = ~9 to ~14 mM, [56]) promote transient increases in intracellular Ca2+ via the Na+/Ca2+ exchanger. Sequential activation of calmodulin, calmodulin kinase 1 (CaMK1), and salt-inducible kinase 1 (SIK1) leads to phosphorylation of a phosphomethylesterase 1 (PME-1), promoting its dissociation from the protein phosphatase 2A (PP2A), which is then activated. Dephosphorylation of the Na+,K+-ATPase α-subunit (NK-inactive) triggers the increase in its catalytic activity (NK-active)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2691526&req=5

Fig4: Salt sensing in mammalian cells.The SIK1 pathway is depicted with its presently known signaling components. Increases in Na+ permeability (from basal = ~9 to ~14 mM, [56]) promote transient increases in intracellular Ca2+ via the Na+/Ca2+ exchanger. Sequential activation of calmodulin, calmodulin kinase 1 (CaMK1), and salt-inducible kinase 1 (SIK1) leads to phosphorylation of a phosphomethylesterase 1 (PME-1), promoting its dissociation from the protein phosphatase 2A (PP2A), which is then activated. Dephosphorylation of the Na+,K+-ATPase α-subunit (NK-inactive) triggers the increase in its catalytic activity (NK-active)
Mentions: The signaling events by which sodium rapidly triggers the activation of SIK1 appear to occur in the proximity of the Na+,K+-ATPase. They are initiated by a parallel influx of calcium (throughout the reverse Na+/Ca2+ exchanger), and are possibly limited to a discrete number of Na+,K+-ATPase units (Fig. 4). A transient rise in intracellular calcium, via the reverse Na+/Ca2+-exchanger, represents the coding signal for the activation of calmodulin kinases (in particular CaMK1) that in turn phosphorylate SIK1 at a threonine residue within its SNH domain (Thr-322). Activated SIK1 does not control Na+,K+-ATPase activity directly through protein phosphorylation (neither the α- nor the β-subunits contain a SIK1 consensus phosphorylation site) but rather by promoting the dephosphorylation of the Na+,K+-ATPase α-subunit. The latter also suggests that dephosphorylation does not result from a direct effect of sodium on Na+,K+-ATPase but rather from a more sophisticated signaling network. The Na+,K+-ATPase constitutively associates with a protein phosphatase 2A (PP2A) [32, 44], and it is logical to think that, if this phosphatase is constantly present in an active form, the Na+,K+-ATPase would never be subjected to phosphorylation, or that this event has to be tightly regulated. Activation of protein phosphatases is not only important for regulating the state of Na+,K+-ATPase subunit phosphorylation [23] but also for regulating the cellular mechanisms responsible for its traffic to and from the plasma membrane [8]. Increases in intracellular sodium result in activation of PP2A, and this effect requires an active SIK1 [44].Fig. 4

Bottom Line: The specific ionic stress (elevated intracellular sodium) is followed by changes in intracellular calcium; the calcium signals are sensed by calcium-binding proteins and lead to activation of SIK1 or SOS2.These kinases target major plasma membrane transporters such as the Na(+),K(+)-ATPase in mammalian cells, and Na(+)/H(+) exchangers in the plasma membrane and membranes of intracellular vacuoles of plant cells.Activation of these networks prevents abnormal increases in intracellular sodium concentration.

View Article: PubMed Central - PubMed

Affiliation: Membrane Signaling Networks, Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital-Solna, Stockholm, Sweden. alejandro.bertorello@ki.se

ABSTRACT
Changes in cellular ion levels can modulate distinct signaling networks aimed at correcting major disruptions in ion balances that might otherwise threaten cell growth and development. Salt-inducible kinase 1 (SIK1) and salt overly sensitive 2 (SOS2) are key protein kinases within such networks in mammalian and plant cells, respectively. In animals, SIK1 expression and activity are regulated in response to the salt content of the diet, and in plants SOS2 activity is controlled by the salinity of the soil. The specific ionic stress (elevated intracellular sodium) is followed by changes in intracellular calcium; the calcium signals are sensed by calcium-binding proteins and lead to activation of SIK1 or SOS2. These kinases target major plasma membrane transporters such as the Na(+),K(+)-ATPase in mammalian cells, and Na(+)/H(+) exchangers in the plasma membrane and membranes of intracellular vacuoles of plant cells. Activation of these networks prevents abnormal increases in intracellular sodium concentration.

Show MeSH
Related in: MedlinePlus