Chapter 17
Tyrosine Protein Kinases and
Adaptive Immunity : TCR, BCR,
Soluble Tyrosine Kinases and NFAT
The family of non-receptor protein tyrosine kinases
There is an important family of receptors that, while possessing no intrinsic catalytic activity, induce responses similar to those of the receptor tyrosine
kinases. They operate by recruiting tyrosine kinases that are either soluble components in the cytosol or are membrane-associated. These are the nonreceptor protein tyrosine kinases (nrPTKs). They can be divided into families based on the sequence of their kinase domains or on the presence of other protein interaction domains (PH, SH3, etc.) (Figure 17.1).1 Recruitment of nrPTKs and the tyrosine phosphorylations that ensue are usually the first steps in the assembly of substantial signalling complexes, consisting of a dozen or more components that bind and interact with each other.
The many abbreviations used in this chapter are collected together at the end of the chapter.
513
Signal Transduction
Fig 17.1 Non-receptor protein tyrosine kinase families.
These are subdivided into 10 families most of which contain SH2 and SH3 domains (Src-A and Src-B families are shown as one). Several were discovered as transforming genes of viral genomes, hence names like Src or Abl, derived from Rous sarcoma virus or Abelson murine leukaemia virus.
Adapted from Robinson et al.1
The receptors that recruit nrPTKs include those that mediate immune responses:
•
•
•
The T lymphocyte receptor (TCR). Involved in the detection of processed antigens, presented in the context of the major histocompatibility complex (MHC). Subsequently it regulates the clonal expansion of T cells.2
The B lymphocyte receptor (BCR). Involved in the detection of non-processed antigens. Important for the elaboration of antigenspecific immunoglobulins necessary for defence against infection by microorganisms.3
The interleukin-2 receptor (IL-2R). The cytokine IL-2, secreted by a subset of T-helper cells, enhances the proliferation of activated T and B cells, increases the cytolytic activity of natural killer (NK) cells and the secretion of IgG.
514