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.