Dataset Information

Regulation of the Golgi apparatus by p38 and JNK kinases during cellular stress responses

ABSTRACT: p38 and JNK are activated in response to acute stress and inflammatory signals. Through modification of a plethora of substrates, these kinases profoundly re-shape cellular physiology for the optimal response to a harmful environment and/or an inflammatory state. Here, we utilized phospho-proteomics to identify several hundred substrates for both kinases. Our results indicate that the scale of signaling from p38 and JNK are of a similar magnitude. Among the many new targets, we highlight the regulation of the transcriptional regulators GIGYF1 and 2 by p38-dependent MK2 phosphorylation and 14-3-3 binding. We also show that the Golgi apparatus contains numerous substrates, and is a major target for regulation by p38 and JNK. When activated, these kinases mediate structural rearrangement of the Golgi apparatus which positively affects protein flux through the secretory system. Our work expands on our knowledge about p38 and JNK signaling with important biological ramifications.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Ana Martinez-Val

LAB HEAD: Jesper V. Olsen

PROVIDER: PXD028151 | Pride | 2021-09-13

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20170516_QE7_nLC3_DBJ_SA_COLLAB_MAX_TMT10phos_2mg_1st_01.raw	Raw
	20170516_QE7_nLC3_DBJ_SA_COLLAB_MAX_TMT10phos_2mg_2nd_02.raw	Raw
	20170516_QE7_nLC3_DBJ_SA_COLLAB_MAX_TMT10phos_2mg_3rd_02.raw	Raw
	20170516_QE7_nLC3_DBJ_SA_COLLAB_MAX_TMT10phos_2mg_4th_02.raw	Raw
	20170516_QE7_nLC3_DBJ_SA_COLLAB_MAX_TMT10phos_2mg_6th_02.raw	Raw

Items per page:

1 - 5 of 7

Publications

Regulation of the Golgi Apparatus by p38 and JNK Kinases during Cellular Stress Responses.

Nordgaard Cathrine C Tollenaere Maxim A X MAX Val Ana Martinez Del AMD Bekker-Jensen Dorte B DB Blasius Melanie M Olsen Jesper V JV Bekker-Jensen Simon S

International journal of molecular sciences 20210904 17

p38 and c-Jun N-terninal kinase (JNK) are activated in response to acute stress and inflammatory signals. Through modification of a plethora of substrates, these kinases profoundly re-shape cellular physiology for the optimal response to a harmful environment and/or an inflammatory state. Here, we utilized phospho-proteomics to identify several hundred substrates for both kinases. Our results indicate that the scale of signaling from p38 and JNK are of a similar magnitude. Among the many new tar ...[more]

PMID: 34502507

Similar Datasets

Project description:Adult skeletal muscle contains resident Muscle Stem Cells (MuSC) with high myogenic and engraftment potentials, making them suitable for cell therapy and regenerative medicine approaches. However, purification process of MuSC remains a major hurdle to their use in the clinic. Indeed, muscle tissue enzymatic dissociation triggers a massive activation of stress signaling pathways, among which P38 and JNK MAPK, associated with a premature loss of MuSC quiescence. While the role of these pathways in the myogenic progression of MuSC is well established, the extent to which their dissociation-induced activation affects the functionality of these cells remains unexplored. We assessed the effect of P38 and JNK MAPK induction on stemness marker expression and MuSC activation state during isolation by pharmacological approaches. MuSC functionality was evaluated by in vitro assays and in vivo transplantation experiments. We performed a comparative analysis of the transcriptome of human MuSC purified with pharmacological inhibitors of P38 and JNK MAPK (SB202190 and SP600125, respectively) versus available RNAseq resources. We monitored PAX7 protein levels in murine MuSC during muscle dissociation and demonstrated a two-step decline partly dependent on P38 and JNK MAPK activities. We showed that simultaneous inhibition of these pathways throughout the MuSC isolation process preserves the expression of stemness markers and limits their premature activation, leading to improved survival and amplification in vitro as well as increased engraftment in vivo. Through a comparative RNAseq analysis of freshly isolated human MuSC, we provide evidence that our findings in murine MuSC could be relevant to human MuSC. Based on these findings, we implemented a purification strategy, significantly improving the recovery yields of human MuSC. Our study highlights the pharmacological limitation of P38 and JNK MAPK activities as a suitable strategy to qualitatively and quantitatively ameliorate human MuSC purification process, which could be of great interest for cell-based therapies.