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PP2A mediates phosphorylation events during shade avoidance response in Arabidopsis

ABSTRACT: Many of shade-intolerant or sun-loving plants grown in close proximity experience a change in light quality and quantity, which leads to transcriptional reprogramming and consequently shade avoidance syndrome (SAS). Despite the importance of phosphorylation-dependent signaling for cellular physiology, the phosphorylation events during SAS are largely unknown. Here, we carried out a survey of shade-regulated protein phosphorylation events by a large-scale mass spectrometry-based quantitative phosphoproteomics approach. The activity of protein phosphatase 2A (PP2A) was specifically activated by shade treatment. Thereinto, shade de-phosphorlated a group of basic leucine zipper (bZIP) transcription factor by PP2A-b’ηθγζ. This study elucidates a previously unidentified mechanism by which the PP2A-bZIPs regulatory module integrates shade signal, and thus uncovers a phosphorylation strategy for the rapid response to changes of environment.

ORGANISM(S): Arabidopsis Thaliana (mouse-ear Cress)

SUBMITTER: Lin, Li

PROVIDER: PXD041796 | JPOST Repository | Thu Apr 25 00:00:00 BST 2024

REPOSITORIES: jPOST

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			Action	DRS
	20210607_HFX_Fudan_Lilin_TMT10_Phosproteomics_SH.raw	Raw
	20210607_HFX_Fudan_Lilin_TMT10_Phosproteomics_WL.raw	Raw
	20210607_HFX_Fudan_Lilin_TMT10_Proteomics_SH.raw	Raw
	20210607_HFX_Fudan_Lilin_TMT10_Proteomics_WL.raw	Raw
	20210728_HFX_Fudan_Lilin_TMT10_Phosproteomics_SH.raw	Raw

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PP2A inhibition instructs spliceosome phosphorylation patterns to create splicing vulnerability in colon adenocarcinoma

Project description:Protein phosphatase 2A (PP2A) is a promiscuous enzyme affecting cellular physiology. It is unclear however, which of the cellular processes are most perturbed upon PP2A inhibition and how such perturbations could be exploited therapeutically. Here, we report an unanticipated sensitivity of the splicing machinery to phosphorylation changes in response to PP2A inhibition by LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. Changed phosphorylation endows LB-100 treated colorectal adenocarcinoma cells with differential splicing patterns. Over 1000 exon skipping and intron retention events in PP2A-inhibited cells affect predominantly regulators of genomic integrity. Finally, LB-100-evoked alternative splicing is predicted to be a source of neoantigens that can improve cancer treatment responses to immune modulators. Our findings provide a potential explanation for the pre-clinical and clinical observations that PP2A inhibition sensitizes cancer cells to immune checkpoint blockade and genotoxic agents.

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Characterization of the C-terminal post-translational modification pattern of the catalytic C subunit of protein phosphatase 2A by mass spectrometry.

Project description:Protein phosphatase 2A (PP2A) is an important regulator of cellular signal transduction pathways. The carboxy-terminal tail of the PP2A catalytic C subunit is thought to be post-translationally modified at three critical sites. Carboxy-terminal methyl-esterification at Leucine 309 is essential for the assembly of most trimeric PP2A complexes. Two phosphorylation sites have been identified at threonine 304 and tyrosine 307. Phosphorylation at Tyr307 has been claimed to inactivate PP2A and has been examined in over 180 studies using commercial antibodies. Yet, surprisingly, Tyr307 phosphorylation has never been identified by mass spectrometry analysis. This fact raised our concern about the existence of this modification in vivo and also about the specificity of antibodies used to detect this modification. For the first time we were able to identify by mass spectrometry phosphorylation of Tyr307 upon transient overexpression of active Src kinase and detected also tyrosine phosphorylation in hemagglutinin (HA) tags. In addition we were able to identify carboxy-terminal methyl-esterification at leucine 309 and also confirmed phosphorylation at threonine 304. Our analysis of commercial antibodies against pTyr307 revealed that none of the tested antibodies shows the designated specificity solely for pTyr307 and thus all data generated by these antibodies need to be revisited.

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PP2A inhibition instructs spliceosome phosphorylation patterns to create splicing vulnerability in colon adenocarcinoma

Project description:Protein phosphatase 2A (PP2A) is a promiscuous enzyme that acts on many aspects of cellular physiology. It remains unclear however, which of the cellular processes are most perturbed upon inhibition of PP2A and how such perturbations could be exploited therapeutically. Here, we report an unanticipated sensitivity of the splicing machinery to phosphorylation changes in response to phosphatase 2A (PP2A) inhibition by LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. These phosphorylation changes endow LB-100 treated colorectal adenocarcinoma cells with differential splicing patterns. Over 1000 exon skipping and intron retention events were enriched in PP2A-inhibited cells affecting the splicing of regulators of genomic integrity and DNA damage response. Finally, alternatively spliced transcripts downstream to LB-100 are predicted to be a source of neoantigens that can improve cancer treatment outcomes in response to immune checkpoint modulators. Collectively, our findings provide a potential explanation for the pre-clinical and clinical observations that inhibition of PP2A results in increased sensitivity of cancer cells to immune checkpoint blockade and DNA damaging agents.

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PP2A is essential for Th17 differentiaiton

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Phosphatase specificity influences the phosphorylation timing of CDK substrates during the cell cycle

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2025-10-05 | PXD060298 | Pride

Intricate coupling between the transactivation and basic-leucine zipper domains governs the CK2-dependent phosphorylation of ATF4

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PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation without affecting PP2A activity.

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