Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.17 (CaMKII)
4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Saccharomyces cerevisiae neutral trehalase (encoded by NTH1) is regulated by cAMP-dependent protein kinase (PKA) and by an endogenous modulator protein. A yeast strain with knockouts of CMK1 and CMK2 genes (cmk1cmk2) and its isogenic control (CMK1CMK2) were used to investigate the role of CaM kinase II in the in vitro activation of neutral trehalase during growth on glucose. In the exponential growth phase, cmk1cmk2 cells exhibited basal trehalase activity and an activation ratio by PKA very similar to that found in CMK1CMK2 cells. At diauxie, even though both cells presented comparable basal trehalase activities, cmk1cmk2 cells showed reduced activation by PKA and lower total trehalase activity when compared to CMK1CMK2 cells. To determine if CaM kinase II regulates NTH1 expression or is involved in post-translational modulation of neutral trehalase activity, NTH1 promoter activity was evaluated using an NTH1-lacZ reporter gene. Similar beta-galactosidase activities were found for CMK1CMK2 and cmk1cmk2 cells, ruling out the role of CaM kinase II in NTH1 expression. Thus, CaM kinase II should act in concert with PKA on the activation of the cryptic form of neutral trehalase. A model for trehalase regulation by CaM kinase II is proposed whereby the target protein for Ca2+/CaM-dependent kinase II phosphorylation is not the neutral trehalase itself. The possible identity of this target protein with the recently identified trehalase-associated protein YLR270Wp is discussed.
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PMID:Evidence for a modulation of neutral trehalase activity by Ca2+ and cAMP signaling pathways in Saccharomyces cerevisiae. 1174 9

IRBIT is a multifunctional protein that controls the activity of various epithelial ion transporters including NBCe1-B. Interaction with IRBIT increases NBCe1-B activity and exposes two cryptic Cl^--sensing GXXXP sites that enable regulation of NBCe1-B by intracellular Cl^- (Cl^- _in). Here, phosphoproteomic analysis revealed that IRBIT controlled five phosphorylation sites in NBCe1-B that determined both the active conformation of the transporter and its regulation by Cl^- _in Mutational analysis suggested that the phosphorylation status of Ser²³², Ser²³³, and Ser²³⁵ was regulated by IRBIT and determined whether NBCe1 transporters are in active or inactive conformations. The absence of phosphorylation at Ser²³², Ser²³³, or Ser²³⁵ produced NBCe1-B in the conformations pSer²³³/pSer²³⁵, pSer²³²/pSer²³⁵, or pSer²³²/pSer²³³, respectively. The activity of the pSer²³³/pSer²³⁵ form was similar to that of IRBIT-activated NBCe1-B, but it was insensitive to inhibition by Cl^- _in The properties of the pSer²³²/pSer²³⁵ form were similar to those of wild-type NBCe1-B, whereas the pSer²³²/pSer²³³ form was partially active, further activated by IRBIT, but retained inhibition by Cl^- _in Furthermore, IRBIT recruited the phosphatase PP1 and the kinase SPAK to control phosphorylation of Ser⁶⁵, which affected Cl^- _in sensing by the ³²GXXXP³⁶ motif. IRBIT also recruited the phosphatase calcineurin and the kinase CaMKII to control phosphorylation of Ser¹², which affected Cl^- _in sensing by the ¹⁹⁴GXXXP¹⁹⁸ motif. Ser²³², Ser²³³, and Ser²³⁵ are conserved in all NBCe1 variants and affect their activity. These findings reveal how multiple kinase and phosphatase pathways use phosphorylation sites to fine-tune a transporter, which have important implications for epithelial fluid and HCO₃ ^- secretion.
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PMID:Modulation of Cl^- signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT. 3037 24

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