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Cell signalling
Cell signalling

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2.3.4 Recruiter receptors

Enzyme-associated or recruiter receptors also form dimers (or oligomers) on activation by their ligand, in a similar way to receptors with intrinsic enzymatic activity. Dimerization facilitates an interaction between the cell surface receptor (which lacks a catalytic domain) and cytosolic proteins with enzymatic activity. In the case of receptors that associate with tyrosine kinases (called ‘tyrosine kinaseassociated receptors’, the most common in this group), it is the non-covalently linked cytoplasmic tyrosine kinase which is autophosphorylated following receptor dimerization. Sometimes homo- or heterodimerization is not sufficient for receptor activation, and activation may follow oligomerization (clustering of several receptors on the membrane) or require membrane-bound co-receptors (structurally unrelated receptors necessary for signal transfer), which may even be RTKs. The end result of the multiplicity of activation combinations for these receptors is that it allows a refinement of signal specificity and diversity, as different downstream effectors are recruited depending on the ligand–receptor complex.

The Src family of tyrosine kinases are the biggest group of kinases that are recruited by tyrosine kinase-associated receptors. One example is Lck (Figure 26). In immune reactions, lymphocyte activation brings together T cell receptors (Figure 5) and other receptors (called ‘CD4’ or ‘CD8’ depending on the activated lymphocyte), which are associated with Lck. Clustering of receptors on the cell surface then results in the tyrosine phosphorylation of the T cell receptor by Lck and activation of downstream signalling pathways. Lck is also very adaptable. As well as associating with CD4 and CD8 receptors, it can also be recruited by means of its SH2 domains to other activated tyrosine kinase (or associated) receptors, thereby strengthening and propagating the signal.

Figure 26 Structure of the SH2 domain of the Src-related kinase Lck, when it is bound to a substrate peptide containing the recognition motif pYEEI. (a) and (b) represent different viewing angles of the same SH2 domain. The substrate peptide backbone is shown as a pink ribbon. The critical amino acid residues are shown in detail as space-filling structures, phosphotyrosine in orange (with attached phosphate groups in red), and isoleucine in blue. (Based on pdb file 1lcj.)