The TEC kinase family has five family members, TEC, BTK, ITK, RLK and BMX, which have similar protein structures and sequence similarities. TEC is the first member identified in this family with high expression in the spleen, kidney, liver and heart. Since many family members exhibit high expression in hematopoietic cells, it is speculated that the TEC kinase family has a function of regulating blood cell processes. The protein structure of the TEC family kinase (Figure. 1) is closely related to the SRC family, all of which constitute a specific N-terminal domain, SH3 (SRC homology 3), SH2 domain and kinase domain. For ITK, BTK and TEC, there is a TEC-homology domain with one or two proline-rich regions (PRR) in front of SH3. The pleckstrin homology domain is a unique structure of the TEC family members of tyrosine kinases that have different specificities for phospholipids. This structure can recruit TEC kinase to the plasma membrane by binding to phospholipids. The atypical TEC kinase RLK does not have a pleckstrin homology domain, but rather has a palmitoylated cysteine residue string that also results in constitutive membrane binding of RLK without binding to phospholipids.
Figure 1. Protein structure of TEC family kinase.
Since TEC, ITK and RLK kinases are present in T cells, it indicates the role of TEC kinase in T cell development. For instance, ITK is a major TEC kinase expressed by naive mouse T cells with less expression of RLK and TEC. During T cell activation, ITK expression is increased in Th2 cells, while expression of RLK is decreased in Th1 cells. BTK is widely expressed in various hematopoietic cells, such as B cells but not t cells. Mice with BTK knockout showed a similar phenotype to xid mice, indicating the role of BTK in B cell signaling.
TEC family kinases (TFKs) are ancient evolutionary kinases that are important and critical for the maturation of hematopoietic cells and the normal development of endothelial cells in mammalian functioning fruit flies. They constitute the second largest family of cytoplasmic tyrosine kinases in humans with five members. Common to all is the function of TFK in intracellular signaling, downstream of cell surface receptors, particularly immune receptors. Receptor-mediated signaling is known to be highly complex in guiding many parallel processes, such as proliferation, programmed cell death, differentiation, migration and secretion. Together, these processes constitute complex and important behaviors of living organisms. Although the first TFK was described 20 years ago, it has taken over many groundbreaking discoveries. We have witnessed the understanding of the identification of new T cell subsets and the key factors in the development of natural killer cells, guiding these two processes through TFKs. Therefore, the first description of TFK mutant tumor patients opens up a new field. At the same time, the role of TFKs in other cell lineages is far from complete. In this series of four small reviews describe various aspects of the paper kinases, seeking their role in the development of T-lymphocytes and natural killer cells, how they function in mast cell biology and how mutations cause human disease to affect TFKs.
1. Liang Y.; et al. Tec family kinases. FEBS Journal, 2011.