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


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