ITAMs Flashcards
ITAM stands for
Immunoreceptor Tyrosine-Based Activation Motif
what are ITAMS
Antigen receptors, Fc receptors and some of the activating receptors of natural killer cells
ITAMS signal via
a common mechanism that is dependent on a conserved amino-aci sequence motif
the conserved amin-acid sequence motif is known as
ITAM
ITAM contains
2 precisely spaced tyrosine within a consensus sequence
when phosphorylated
the tyrosine’s provide a binding site for one or to closely related intracellular tyrosine kinases
which intracellular tyrosine kinases are provided a bindings site on the ITAM?
SYK in most immune cells
ZAP-70in T cells
both Syk and ZAP-70 have
tandem SH2 domains (src homology 2) evenly spaced at exactly the right distance apart to cock onto the two phosphotyrosines which activate signalling events downstream of the receptor
signal transduction by ITAM-containing immunoreceptors
1) The surface immunoglobulin (Ig)that serves as the B cell receptor for antigen brings the receptor into proximity with a Src-family tyrosine kinase, which is held in the plasma membrane by a lipid tail and phosphorylates ITAM tyrosines in the receptor Iga and Igb chains
2) This creates a binding site for Syk, which binds to the doubly phosphorylated ITAM sequence
3) Once bound, Syk becomes activated by tyrosine phosphorylation and it then phosphorylates other signaling proteins that ultimately bring about changes in the behaviour of the cell e.g. antibody production