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Proteomics of 24 h TCR activated wild-type and Pim1/Pim2 double knockout CD4 and CD8 T cells

ABSTRACT: T cell antigen-receptor (TCR) and cytokine receptor engagement trigger large changes in Serine/Threonine kinase signalling networks to drive T cell activation and differentiation. The role of only few kinase signalling pathways have been studied in detail, and in this context, Pim kinases are an interesting, yet understudied, family of Serine/Threonine kinases, with reported roles in key processes including survival, proliferation, metabolism across a range of cell types. T lymphocytes predominantly express PIM1 and PIM2, which are rapidly induced by TCR, costimulation and cytokine signalling. Using high-resolution mass spectrometry we systematically examine the impact of Pim1/Pim2 double deficiency downstream of initial TCR engagement. We find that Pim kinases are dispensable for TCR-driven T cell activation and have little impact on the total proteome in these cells.

INSTRUMENT(S): LTQ Orbitrap Velos Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell, Lymph Node

SUBMITTER: Laura Spinelli

LAB HEAD: Professor Doreen

PROVIDER: PXD051198 | Pride | 2024-04-15

REPOSITORIES: Pride

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			Action	DRS
	ExperimentalDesignTemplate.txt	Txt
	JM1.raw	Raw
	JM10.raw	Raw
	JM11.raw	Raw
	JM12.raw	Raw

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Whole Proteomics of 24 hr pan Pim kinase inhibitor treatment of IL2 cultured CD8 T cells

Project description:T cell antigen-receptor (TCR) and cytokine receptor engagement trigger large changes in Serine/Threonine kinase signalling networks to drive T cell activation and differentiation. The role of only few kinase signalling pathways have been studied in detail, and in this context, Pim kinases are an interesting, yet understudied, family of Serine/Threonine kinases, with reported roles in key processes including survival, proliferation, metabolism across a range of cell types. T lymphocytes predominantly express PIM1 and PIM2, which are rapidly induced by TCR, costimulation and cytokine signalling. Using single shot DDA mass spectrometry we examine the impact of 24 hours treatment with two different pan-Pim kinase inhibitors PIM447 and AZD1208 on in vitro IL2 differentiated effector cytotoxic T lymphocytes. The Jak1/3 inhibitor tofacitinib was included as a control as this also blocks production of Pim kinases downstream of IL2. We find that treatment with pan-Pim kinase inhibitors has a similar phenotype to Pim1/Pim2 double deficiency, showing a reduction in proteins that are key for effector cell function: glucose transporters SLC2A1 and SLC2A3 and key effector molecule Granzyme B and an increase in the translational repressor PDCD4.

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