Data on peptides identified by mass spectrometry analysis of in vitro DYRK1A-mediated phosphorylation sites on GLI1

Ehe, Ben K.; Lamson, David R.; Tarpley, Michael; Onyenwoke, Rob U.; Graves, Lee M.; Williams, Kevin P.

doi:10.1016/j.dib.2017.09.057

Cited by 3 publications

(11 citation statements)

References 4 publications

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“…Phosphorylation was observed on serine (Ser) and threonine (Thr) residues with a predominance for Ser, agreeing with previous observations that DYRK1A has a preference for Ser over Thr [22]. The phospho-peptides identified by at least 4 PSM (peptide spectrum matches) are detailed in Table 2 in [18]. …”

Section: Resultssupporting

confidence: 88%

“…Gel slices were treated with trypsin to generate tryptic peptides, phospho-peptides enriched by TiO 2 beads and analyzed by mass spectrometry. Details on sequence coverage and all phospho-peptides identified across all samples are detailed in the accompanying Data in Brief article [18]. Based on the GLI1 sequence from NCBI (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Based on the GLI1 sequence from NCBI (Supplementary Fig. 1), approximately 50-70% coverage was observed and between 76 to 161 peptides identified for the samples (see Table 1 in [18]). A number of high confidence phospho-peptides were identified with the majority present in all samples, suggesting those were related to basal GLI1 phosphorylation.…”

Section: Resultsmentioning

confidence: 99%

“…This phosphorylated peptide was detected 6 times in each of the analyses of sample 2 (Fig. 2A and Table 3 in [18]) but not in any other run. In contrast, the unphosphorylated peptide (APSISTVEPK) was detected in all samples at ∼10 to 13 times per run (see Table 3 in [18].…”

Section: Resultsmentioning

confidence: 99%

“…Detailed methodology is described in the accompanying Data in Brief article [18]. Briefly, gel slices were divided into two pieces and each piece treated with reducing agent, alkylated and digested with trypsin.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1

Ehe

Lamson

Tarpley

et al. 2017

Biochemical and Biophysical Research Communications

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GLI1 is a key downstream transcription effector of the Hedgehog (Hh) signaling pathway that is involved in promoting cell growth, differentiation and tissue patterning in embryonic development. GLI1 over-activation and its nuclear localization has also been linked to the increased aggressiveness of a number of cancers. It has previously been demonstrated that DYRK1A (dual-specificity tyrosine-regulated kinase 1A) can phosphorylate GLI1 and promote GLI1 nuclear localization and its transcriptional activity. Utilizing recombinant human GLI1 and DYRK1A proteins and phospho-peptide mass spectrometry, we demonstrated that GLI1 is phosphorylated by DYRK1A at Ser408, a phospho-site that falls within the putative nuclear localization sequence (NLS) of GLI1 suggesting a possible mechanistic role in modulating its translocation. Further, we showed that the Ser408 site on GLI1 was not phosphorylated in the presence of the selective DYRK1A inhibitor harmine. The data described herein provide the first identification of a DYRK1A-mediated site of phosphorylation on GLI1 within its NLS and may serve as a valuable mechanism for further understanding Hh signaling modulation.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1

Ehe

Lamson

Tarpley

et al. 2017

Biochemical and Biophysical Research Communications

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Recent research and development of DYRK1A inhibitors

Zhao

Xiong

Liu

et al. 2022

Chinese Chemical Letters

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CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury

et al. 2020

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Proteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases. Carboxyl terminus of Hsc70-interacting protein (CHIP) is an important regulator of proteostasis in many cells, having E3-ligase and chaperone functions and often directing damaged proteins towards proteasome recycling. While enhancing CHIP functionality has broad therapeutic potential, prior efforts have all relied on genetic upregulation. Here we report that CHIP-mediated protein turnover is markedly post-translationally enhanced by direct protein kinase G (PKG) phosphorylation at S20 (mouse, S19 human). This increases CHIP binding affinity to Hsc70, CHIP protein half-life, and consequent clearance of stress-induced ubiquitinated-insoluble proteins. PKG-mediated CHIP-pS20 or expressing CHIP-S20E (phosphomimetic) reduces ischemic proteo- and cytotoxicity, whereas a phospho-silenced CHIP-S20A amplifies both. In vivo, depressing PKG activity lowers CHIP-S20 phosphorylation and protein, exacerbating proteotoxicity and heart dysfunction after ischemic injury. CHIP-S20E knock-in mice better clear ubiquitinated proteins and are cardio-protected. PKG activation provides post-translational enhancement of protein quality control via CHIP.

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Data on peptides identified by mass spectrometry analysis of in vitro DYRK1A-mediated phosphorylation sites on GLI1

Cited by 3 publications

References 4 publications

Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1

Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1

Recent research and development of DYRK1A inhibitors

CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury

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