FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin

Schytte, Gitte N; Christensen, Brian; Bregenov, Ida; Kjøge, Katarzyna; Scavenius, Carsten; Petersen, Steen V.; Enghild, Jan J.; Sørensen, Esben S.

doi:10.1002/jcb.29708

Cited by 14 publications

(28 citation statements)

References 34 publications

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“… 21 Moreover, Schytte et al recently reported that the phosphorylation of an OPN construct, which covers the integrin binding motif, and full-length OPN, co-expressed with Fam20C, strongly hampers the interaction with α v β 3 integrin. 66 OPN is not only the most phosphorylated substrate of Fam20C but also a natural binder to integrin receptors. 48 Thus, its phosphorylation may have a major impact on the mediation of cell–ECM adhesion properties through integrin binding.…”

Section: Resultsmentioning

confidence: 99%

“…Thereby, it abolishes energetically favorable interactions between OPN sites that are distant from the canonical RGD motif and integrin receptors. 48 , 66 However, the central part that contains the (integrin binding) RGD motif (residues 159–161) retains its local rigidity ( 15 N R 2 rates) and maintains a preformed template for receptor recognition.…”

Section: Resultsmentioning

confidence: 99%

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Hyperphosphorylation of Human Osteopontin and Its Impact on Structural Dynamics and Molecular Recognition

et al. 2021

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Protein phosphorylation is an abundant post-translational modification (PTM) and an essential modulator of protein functionality in living cells. Intrinsically disordered proteins (IDPs) are particular targets of PTM protein kinases due to their involvement in fundamental protein interaction networks. Despite their dynamic nature, IDPs are far from having random-coil conformations but exhibit significant structural heterogeneity. Changes in the molecular environment, most prominently in the form of PTM via phosphorylation, can modulate these structural features. Therefore, how phosphorylation events can alter conformational ensembles of IDPs and their interactions with binding partners is of great interest. Here we study the effects of hyperphosphorylation on the IDP osteopontin (OPN), an extracellular target of the Fam20C kinase. We report a full characterization of the phosphorylation sites of OPN using a combined nuclear magnetic resonance/mass spectrometry approach and provide evidence for an increase in the local flexibility of highly phosphorylated regions and the ensuing overall structural elongation. Our study emphasizes the simultaneous importance of electrostatic and hydrophobic interactions in the formation of compact substates in IDPs and their relevance for molecular recognition events.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Hyperphosphorylation of Human Osteopontin and Its Impact on Structural Dynamics and Molecular Recognition

et al. 2021

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“…Next, we determined how could SPP1, a secreted protein, function through PKCα. Previous studies have reported that SPP1 interacted with many cell types via various receptors, including CD44 and integrins (αvβ3, αvβ1, αvβ5, αvβ6, α8β1, α5β1, α9β1, and α4β7) [14,34]. However, receptors have been reported to be expressed on SCs including CD44, αvβ3, αvβ8, α1β1, α2β1, α6β1 and α7β1 [31,32].…”

Section: Cd44 and αVβ3 Were Upregulated In Scs After Sciatic Nerve Inmentioning

confidence: 98%

SPP1 promotes Schwann cell proliferation and survival through PKCα by binding with CD44 and αvβ3 after peripheral nerve injury

Wang

Zhang

et al. 2020

Cell Biosci

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Background: Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results: SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3. Conclusion: These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

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“…CD44 and αvβ3 were upregulated in SCs after sciatic nerve injury in rats Next, we determined how could SPP1, a secreted protein, function through PKCα. Previous studies have reported that SPP1 interacted with many cell types via various receptors, including CD44 and integrins (αvβ3, αvβ1, αvβ5, αvβ6, α8β1, α5β1, α9β1, and α4β7) [14,34]. However, receptors have been reported to be expressed on SCs including CD44, αvβ3, αvβ8, α1β1, α2β1, α6β1 and α7β1 [31,32].…”

Section: Spp1 Promoted Sc Proliferation and Inhibited Apoptosis Throumentioning

confidence: 98%

SPP1 Promotes Schwann Cell Proliferation and Survival through PKCα by Binding with CD44 and αvβ3 after Peripheral Nerve Injury

Wang

Zhang

et al. 2020

Preprint

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Abstract Background: Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results: SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3. Conclusion: These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

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FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin

Cited by 14 publications

References 34 publications

Hyperphosphorylation of Human Osteopontin and Its Impact on Structural Dynamics and Molecular Recognition

Hyperphosphorylation of Human Osteopontin and Its Impact on Structural Dynamics and Molecular Recognition

SPP1 promotes Schwann cell proliferation and survival through PKCα by binding with CD44 and αvβ3 after peripheral nerve injury

SPP1 Promotes Schwann Cell Proliferation and Survival through PKCα by Binding with CD44 and αvβ3 after Peripheral Nerve Injury

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