Phosphorylation of annexin II tetramer by protein kinase C inhibits aggregation of lipid vesicles by the protein.

Johnstone, Sharon A.; Hubaishy, I.; Waisman, David M.

doi:10.1016/s0021-9258(18)35704-1

Cited by 93 publications

(30 citation statements)

References 49 publications

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“…Addition of both S100A10 and S100A4 to NTD-containing ANXA2 variants decreased the average EC 50 of Ca 2+ from about 400 mM to 50 and 200 mM, respectively (Figure 5E (Table S4)). Note that even in the presence of S100A10 the EC 50 values were in the 10 mM range, significantly exceeding the previously published values (Ayala-Sanmartin et al, 2000;Drust and Creutz, 1988;Johnstone et al, 1992). This difference might derive from different buffer conditions (pH, salt concentration, type of the reducing agent), as well as from the different source and sequence of the ANXA2 protein.…”

Section: Regulation Of Anxa2-mediated Luv Bridging By Phosphorylation and S100 Bindingcontrasting

confidence: 60%

“…is known to be modulated by PKC phosphorylation or phosphomimicking amino acid substitutions (Ayala-Sanmartin et al, 2000;Johnstone et al, 1992). With native ANXA2, the EC 50 value of Ca 2+ was about 160 mM, which increased to 300 and 900 mM with ANXA2 S26E and ANXA2 S12EÀS26E , respectively (Figure 5D and Table S4).…”

Section: Regulation Of Anxa2-mediated Luv Bridging By Phosphorylation and S100 Bindingmentioning

confidence: 98%

“…In any case, these interactions could interfere not only with membrane crosslinking, but also with the binding of S100 proteins. Since the hydration shell of Glu is smaller than that of the phosphorylated Ser and bears only a single negative charge, these ionic interactions should be weaker in ANXA2 S12EÀS26E than in the PKC-phosphorylated protein, which could explain the lower extent of inhibition induced by the double phosphomimicking substitution than by the effective PKC phosphorylation (Ayala-Sanmartin et al, 2000;Johnstone et al, 1992). To confirm this hypothesis, further high-resolution 3D structural works should be conducted with ANXA2 phosphorylated at positions 12 and 26.…”

Section: Regulation Of Anxa2-mediated Membrane Bridging By Phosphorylation and Pseudo-phosphorylationmentioning

confidence: 99%

“…Based on the crystal structures of ANXA4 and its phosphomimicking Thr6Asp mutant, phosphorylation of Thr6 results in the dislocation of the NTD, which leads to impaired ANXA4-mediated membrane aggregation (Kaetzel et al, 2001). Regarding ANXA2, the mutually exclusive phosphorylation of Ser12 and Ser26 by PKC (Gould et al, 1986;He et al, 2011;Jost and Gerke, 1996) and Tyr24 by c-Src (Erikson and Erikson, 1980) negatively regulates the ANXA2-dependent membrane aggregation (Ayala-Sanmartin et al, 2000;Hubaishy et al, 1995;Johnstone et al, 1992). However, no structural data for the phosphorylated ANXA2 is available.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of the Equilibrium between Closed and Open Conformations of Annexin A2 by N-Terminal Phosphorylation and S100A4-Binding

et al. 2017

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Annexin A2 (ANXA2) has a versatile role in membrane-associated functions including membrane aggregation, endo- and exocytosis, and it is regulated by post-translational modifications and protein-protein interactions through the unstructured N-terminal domain (NTD). Our sequence analysis revealed a short motif responsible for clamping the NTD to the C-terminal core domain (CTD). Structural studies indicated that the flexibility of the NTD and CTD are interrelated and oppositely regulated by Tyr24 phosphorylation and Ser26Glu phosphomimicking mutation. The crystal structure of the ANXA2-S100A4 complex showed that asymmetric binding of S100A4 induces dislocation of the NTD from the CTD and, similar to the Ser26Glu mutation, unmasks the concave side of ANXA2. In contrast, pTyr24 anchors the NTD to the CTD and hampers the membrane-bridging function. This inhibition can be restored by S100A4 and S100A10 binding. Based on our results we provide a structural model for regulation of ANXA2-mediated membrane aggregation by NTD phosphorylation and S100 binding.

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Section: Regulation Of Anxa2-mediated Luv Bridging By Phosphorylation and S100 Bindingcontrasting

confidence: 60%

Section: Regulation Of Anxa2-mediated Luv Bridging By Phosphorylation and S100 Bindingmentioning

confidence: 98%

Section: Regulation Of Anxa2-mediated Membrane Bridging By Phosphorylation and Pseudo-phosphorylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of the Equilibrium between Closed and Open Conformations of Annexin A2 by N-Terminal Phosphorylation and S100A4-Binding

et al. 2017

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“…Ser25 side chain of ANXA2 is a potential PKC phosphorylation site. 31,47 To investigate ANXA2 phosphorylation by PKC, in vitro PKC phosphorylation assays were performed (Figure 2a). The amount and purity of loaded GST, GST-ANXA2, and GST-TIMAP proteins were confirmed by SDS-PAGE.…”

Section: Phosphorylation State Of Ser25 In Anxa2 Is Regulated By Pkc and Timap-pp1cmentioning

confidence: 99%

Dephosphorylation of annexin A2 by protein phosphatase 1 regulates endothelial cell barrier

et al. 2021

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Annexin A2 (ANXA2) is a multifunctional protein expressed in nearly all human tissues and cell types, playing a role in various signaling pathways. It is subjected to phosphorylation, but no specific protein phosphatase has been identified in its posttranslational regulation yet. Using pull-down assay followed by liquid chromatography-mass spectrometry analysis we found that ANXA2 interacts with TIMAP (TGF-beta-inhibited membrane-associated protein) in pulmonary artery endothelial cells. TIMAP is highly expressed in endothelial cells, where it acts as a regulatory and targeting subunit of protein phosphatase 1 (PP1). TIMAP plays an important role in the regulation of the endothelial barrier maintenance through the dephosphorylation of its several substrate proteins. In the present work, phosphorylation of Ser25 side chain in ANXA2 by protein kinase C (PKC) was shown both in vivo and in vitro. Phosphorylation level of ANXA2 at Ser25 increased greatly by inhibition of PP1 and by depletion of its regulatory subunit, TIMAP, implying a role of this PP1 holoenzyme in the dephosphorylation of ANXA2. Immunofluorescence

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Metalloproteomics

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Phosphorylation of annexin II tetramer by protein kinase C inhibits aggregation of lipid vesicles by the protein.

Cited by 93 publications

References 49 publications

Regulation of the Equilibrium between Closed and Open Conformations of Annexin A2 by N-Terminal Phosphorylation and S100A4-Binding

Regulation of the Equilibrium between Closed and Open Conformations of Annexin A2 by N-Terminal Phosphorylation and S100A4-Binding

Dephosphorylation of annexin A2 by protein phosphatase 1 regulates endothelial cell barrier

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