T cell transcription factors Flashcards
How does the CD4/8 transduce the signal?
Lkc associated tyrosine kinase in the cytosol phosphorylates ITAMs on the ZETAs: this provides a binding site for ZAP-70
ZAP-70 binds, is phosphorylated by Lck
ZAP-70-P is now a binding site for LATs, which phosphorylate PLC initiates downstream signaling
PLC –>
IP3 —————> PKC ——-> IkB inactivation —> NFkB activation —> IL-2 gene
PKC —>
inactivates IkB, which in turn releases NFkB
NFkB —>
transcription factor that activates IL-2 gene
RAS and MAP —>
AP-1 activation via Ca influx
AP-1
transcription factor to synthesize IL-2
NFkB —>
IL-2 synthesis
activated by PKC, which inactivates IkB, which is iniaited by PLC
AP-1 –>
IL-2 synthesis
activated by Ras-MAP PWs
How is IkB inactivated?
ubiquination
Signal 2
Cd28–CD80/86 T cell – APC
Signal 1 w/out costimulation
APC–TCR+No Co Stim –> NFAT (transcription factor)—> Anargy inducing signal
Signal 1 w/costimulation
Signal 1 (TCR) + Signal 2 (Costim)
Sig 1 –> NFkB
Sig 2 –> NFAT
NFAT + NFkB –> reproductive response
P13, PDK1, and AKT in T cell activation: first, what’s the point?
the point is inactivating apoptotic proteins
P13, PDK1, and AKT in T cell activation: how does it work?
It works via P13 kinase: converts PIP2 –> PIP3
PIP3 activates PDK-1: PDK activates AKt
P13, PDK1, and AKT in T cell activation: the “train” of events superficially
P13K activates PIP2 –> PIP3 –> PDK-1 –> Akt –> cell survival