Monomer (By similarity). Interacts with ARRB2, AXIN1, CABYR, DISC1, MMP2, MUC1, NIN and PRUNE (By similarity). Interacts with AXIN1; the interaction mediates hyperphosphorylation of CTNNB1 leading to its ubiquitination and destruction. Interacts with and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal domain) (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B.
Function:
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity.
Subcellular Location:
Cytoplasm
Nucleus
Membrane
Cell membrane
The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosophorylated form to the cell membrane.
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s
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Precision
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Intra-assay Precision (Precision within an assay):Three samples of known concentration were tested twenty times on one plate to assess intra-assay precision.
Intra-Assay CV: ≤3.9%
Inter-assay Precision (Precision between assays):Three samples of known concentration were tested in five separate assays to assess inter-assay precision.
Inter-Assay CV: ≤7.7%
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Recovery
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Recovery was determined by spiking various levels of ACE into serum and plasma .
Sample Type
Average(%)
Recovery Range(%)
Serum
99
91-103
Plasma
98
93-106
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Linearity
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The linearity of the kit was assayed by testing samples spiked with appropriate concentration of ACE and their serial dilutions. The results were demonstrated by the percentage of calculated concentration to the expected.
Sample
1:2
1:4
1:8
1:16
serum(n=5)
92-105%
90-101%
95-105%
92-109%
EDTA plasma(n=5)
89-95%
93105%
89-94%
90-106%
heparin plasma(n=5)
93-104%
94-110%
101-111%
91-110%
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[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: PHOSPHORYLATION AT TYR-216;MUTAGENESIS OF TYR-216
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: SUBCELLULAR LOCATION;IDENTIFICATION IN A COMPLEX WITH MACF1; APC; AXIN1 AND CTNNB1
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION IN REGULATION OF PANCREATIC BETA-CELLS
[15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s)
Cited for: FUNCTION IN PHOSPHORYLATION OF MARK2;MUTAGENESIS OF SER-9
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