Introduction
BLK is one of the important members of the SRC family kinases (SFKs). In human, there are eight closely related non-receptor tyrosine kinases of SFKs includes SRC, YES1, FYN, FGR, LCK, LYN, HCK and BLK. These all kinases are related to each other as they all possess quite similar domain structures including N-terminal segment that includes the SH4 domain and 50-70 additional residues that are different to each family member (Oda, Kumar, & Howley, 1999). All are differentiated by SH3 and an SH2 regulatory domains N-terminal to the catalytic kinase domain. The SFKs are linked with the transmembrane receptors and turn on by extracellular receptor stimulation (Petersen et al., 2017). The SFKs are tightly regulated, it exhibits little activity in normal cells in the absence of regulatory signal. This regulation is mediated by phosphorylation/dephosphorylation of a specific tyrosine residue in the carboxy-terminal tail (Tyr 527 in c-Src). Regulatory tyrosine residue is phosphorylated by means of cytoplasmic tyrosine kinase which includes Csk causes a conformational exchange that effects within the closed-form of c-Src due to an intramolecular bonding among the phosphorylated tyrosine and SH2 domains. Due to closed conformation, Src could now not have interaction with different targeted proteins thru SH2 and SH3 domain. After dephosphorylation of Tyr 527, Src embraces an active (open) conformation in which the SH2 and SH3 domains are allowed to have interaction with some other goal. Inactive conformation, the kinase area of Tyr 416 is obtainable for autophosphorylation, for growing the kinase activity (Oda et al., 1999).
It has been shown that BLK, similar to other members of the Src group of tyrosine kinases (such as Lyn), interacts with BANK1, an adaptor/scaffold protein primarily expressed in B cells (Castillejo-López et al., 2012). Recently, various genome-wide association studies (GWAS) identified different single nucleotide polymorphisms (SNPs) in BLK (rs13277113A/G and rs2736340T/C) and BANK1 (rs10516487C/T R61H and rs3733197G/A A383T) to be associated with systemic lupus erythematosus (SLE), firstly in European and Asian-derived populations(Ramírez-Bello et al., 2019). Tumour necrosis factor receptor superfamily 4 (TNFSF4) part of TNF superfamily, and is expressed on dendritic cells, macrophages, cluster of differentiation (CD)4+/CD8+ T cells, activated NK cells and other cells (Murata et al., 2000). Recently research showed that gene‑degree interaction among BLK and TNFSF4 may additionally display a synergistic effect on T cells and B cells thru the nuclear signalling NF‑kB pathway, and this can describe the function in figuring out the immunologic aberration (Shen et al., 2017).
BLK entails in signal transduction downstream of the B‑cellular receptor; subsequently, it might affect the proliferation and differentiation of B cells. (Harley et al., 2008). For example, SRC is an oncogene concerned in several malignancies which include breast, lung, colon and pancreatic most cancers (Summy & Gallick, 2003). Recently it is shown that the active human blk has an oncogenic property to induce tumours in mice (Petersen et al., 2017). Transgenic mice expressed constantly active murine Blk in their lymphoid organ developed lymphomatous B- and T-cell-like disorders confirming a transforming potential of orthologue murine (Malek et al., 1998).
The works, however, have never been reviewed. Here, we will try to relate with the function, and their motif is conserved or not, we have compiled for the first time a detailed analysis of all the relevant information for BLK that may be helpful in the understanding of functional importance of BLK in the body system.