Signal Transduction via Integrins

2 Intracellular Signal Molecules of the T and B Cell Antigen Receptors 

The T and B cell antigen receptors do not have any intrinsic protein tyrosine kinase activity. Rather, antigen binding leads to recruitment and activation of protein tyrosine kinases on the cytoplasmic side of the receptor. Probably, coupling of the tyrosine kinase takes place via the ARAM motif directly. 

In this reaction chain, ZAP kinase performs an essential function. Tlie phosphorylated ARAM motives recruit ZAP70 kinase to the T cell receptor complex and mediate high affinity binding to the kinase. The two SH2 domains of ZAP70 kinase bind in tandem fashion to the twice-phosphorylated ARAM motif ZAP70 kinase shows a complex pattern of Tyr phosphorylation, including phosphorylations with an inhibitory effect. 

An inhibitory phosphorylation of the tyrosine kinases Lck and Fyn is also important for signal transduction, and this is performed by Csk kinase. This phosphorylation takes place at the C-terminus of Lck and inhibits the kinase activity in a similar way to that already structurally illustrated for Src kinase (see 8.3.2). 

The further com e of signal transduction is variable. The following signaling pathways are activated following stimulation of T cell receptors  

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Mould, A. P., Barton, S. J., Askari, J. A., McEwan, P. A., Buckley, P. A., Craig, S. E., and Humphries, M.J. (2003b). Conformational changes in the integrin j3A domain provide a mechanism for signal transduction via hybrid domain movement. / Biol. Chem. 278, 17028-17035. 

Figure2 Model of collagen-induced signal transduction via the collagen receptors a2pi integrin and GPVI/FcRy...

Adhesion molecules are indispensable components of nervous tissue. They adhere cell membranes to each other with varying degrees of strength and translate adhesion into cellular responses via signal-transduction pathways (see, for example, [45]). The major classes of adhesion molecules, the integrins, IgCAMs and cadherins, act cooperatively [46] and in concert to coordinate brain development and maturation and, in adulthood, to maintain the normal tissue architecture. 

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