The transduced signal

Protein tyrosine kinases and phosphatases

The principal structural unit that regulates coupling of the TCR to downstream signal transduction is termed the immunoreceptor tyrosine-based activation motif (ITAM) or alternatively, antigen recognition activation motif (ARAM) (Figure 1). Each IT AM consists of two YXXL/I repeats separated by 6-8 residues. There are one each in the cytoplasmic domains of CD3y, 8, e and three in the TCR£ chain (£1, ¿2 and £3). Since each TCR can contain a TCR£ dimer and two CD3 dimers (eS and ey), each TCR can contain a total of 10 ITAMS. This is many more than are present in other lymphocytes such as B cells, natural killer (NK) cells and mast cells. The first biochemical event that has been measured following the triggering of the human T cell receptor is the activation of protein tyrosine kinases (PTKs), enzymes that phosphorylate tyrosine residues in proteins. This is observed as an increase in the phosphate content of several tyrosine-containing proteins and occurs within 5 s of stimulation of the TCR. At least three families of PTKs are associated with the TCR. Two hTCRÇI hTCRÇ2 hTCRÇ3

hCD3y hCD3S mCD3e mlgct mlgß

hlgE FcFW hlgE FcRß

BLV gp30 EBV-LMP2A

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