Chapter 11: Lymphocyte Activation Flashcards
ITAM’s
Signalling subunits
Phosphorylation by Src (lck) leads to TCR activation
Src family kinase
E.g. lck
Phosphorylate ITAM’s which leads to TCR activation
Csk
C terminal src kinase
Phosphorylation of Lck (blocks SH2 domain) which leads to its inactivation
CD45
Phosphatase which removes phosphate from lck and leads to its activation
Tyrosine 505
Blocks the active site of SH2 domain on lck
Tyrosine 394
Phosphorylation leads to open SH2 domain
Lck
A src family kinase which phosphorylates ITAMS
Also phosphorylates ZAP70
ZAP70
Syk family kinase
Recruited to ITAM of CD3Zeta
Phosphorylates LAT and PLCGamma
LAT
When phosphorylated by Zap70 acts as a docking site
Phosphortylated tyrosines are the docking site
Leads to PLC pathway (NFkB, NFAT) and MAP kinase pathway
PLCGamma
Activated by Zap 70 and Itk
When cleaved leads to DAG and IP3
Leads to PLC pathway resulting in NFkB or NFAT
IkB kinase
Phosphorylates NFkB/IkB compex which leads to dissociation of IkB and allows NFkB to be translocated to nucleus
PKC
Protein kinase C
Product from DAG which leads to recruitment of IkB kinase which dissociates IkB/NFkB compex
DAG
Formed from the cleavage of PLC Gamma
IP3
Formed from cleavage of PLC gamma and leads to NFAT transcription factor activation
Mobilises calcium stores required to activate calcineurin
Calcineurin
Phosphatase which removes phosphate from inactive NFAT
Attached to Calmodulin and is activated which Ca2+ binds to calmodulin
Allows NFAT translocation to nucleus