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Printable Handouts
Navigable Slide Index
- Introduction
- Acknowledgements
- T cell development and function
- T cell activation
- From nave to activated cytotoxic T cells (1)
- Immune activation regulates different processes
- From nave to activated cytotoxic T cells (2)
- Primary T cells express approx. 24,566 genes
- The key question
- The immunological synapse
- T cell activation: lots of receptors
- Our focus is the serine kinase networks
- The human kinome
- How complex is the T cell phosphoproteome?
- Identification of serine threonine phosphorylations
- Kinases predicted to be active in CTL (1)
- Functions of the CTL phosphoproteins
- Serine/ threonine kinases in T cell biology
- Kinases predicted to be active in CTL (2)
- PKB signal transduction
- Tools to probe PI3K/PDK1/PKB's role in CTL
- Inhibitors prevent phosphorylation of PKB in CTL
- AktI 1/2 blocks phosphorylation and activity of PKB
- Deletion of PDK1 blocks PKB/Akt activation
- What is the role of PKB/Akt in CTL?
- CTL express approximately 9405 genes
- Inhibition of PKB and decrease in cytolytic effectors
- Inhibition of PKB and downregulation of perforin
- PKB determines repertoire of cytokine receptors
- PKB increases expression of CD62L and CCR7
- What are CCR7 and CD62L?
- Primary naive T cells
- CD62L and CCR7 direct lymphocyte transmigration
- CTL lose expression of CCR7 and CD62L
- CD62L and CCR7 in naive/ memory and CD8 T cells
- CD62L and CCR7 mRNA expression
- PKB inhibition restores CD62L and CCR7
- Can PKB inhibition reprogram T cell trafficking?
- In vivo homing experiments
- CTL treated with PKB inhibitor regain homing ability
- Will PIP3 & PKB activation switch off CCR7,CD62L?
- How to get increased PIP3 and PKB activation
- PTEN deletions/downregulation occur in tumours
- Producing CTL that lack both PTEN and PDK1
- PTEN deletion stimulates PKB activity via PDK1
- PTEN deletion de-regulates adhesion, chemokines
- PTEN-null T cells don't home to lymphoid organs
- PKB required to switch off CD62L & CCR7
- PKB phosphorylates Foxo1 and Foxo3A
- Does non phosphorylatable Foxo restore CD62L?
- Phosphorylated Foxo restores CD62L expression
- How does Foxo control CD62L & CCR7 expression
- PKB activity down-regulates KLF2 mRNA (1)
- PKB activity down-regulates KLF2 mRNA (2)
- Inhibition of PI3K or PKB restores KLF2 expression
- Re-expression of KLF2 in CTL upregulates CD62L
- PKB cascade and KLF2
- PKB controls T cell trafficking via Foxo
- Summary of nave vs. cytotoxic cells
- Serine kinase are important in T cells
- Many more genes to work on
Topics Covered
- T cell development and function
- T cell activation
- Serine kinase networks
- T cell phosphoproteome
- Kinases active in CTL
- Functions of the CTL phosphoproteins
- PKB signal transduction
- PKB/Akt role in CTL
- Inhibition of PKB
- CCR7 and CD62L
- Homing ability in CTL
- PIP3 & PKB activation
- PTEN deletion/down-regulation effect
- PKB phosphorylates Foxo1 and Foxo3A
- Foxo and CD62L & CCR7 expression
- PKB cascade and KLF2
- PKB controls T cell trafficking via Foxo
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Talk Citation
Cantrell, D. (2011, August 15). Serine kinases and T lymphocyte biology [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 7, 2024, from https://doi.org/10.69645/ZHFM5960.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Doreen Cantrell has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.