Abstract
Downstream of kinase (Dok) 3 is a member of the Dok family of adaptor proteins known to regulate signaling pathways downstream of various immunoreceptors. As Dok-3 lacks intrinsic catalytic activity, it functions primarily as a molecular scaffold to facilitate the nucleation of protein complexes in a regulated manner and hence, achieve specificity in directing signaling cascades. Since its discovery, considerable progress has been made toward defining the role of Dok-3 in limiting B cell-receptor signaling. Nonetheless, Dok-3 has since been implicated in the signaling of Toll-like and C-type lectin receptors. Emerging data further demonstrate that Dok-3 can act both as an activator and inhibitor, in lymphoid and non-lymphoid cell types, suggesting Dok-3 involvement in a plethora of signal transduction pathways. In this review, we will focus on the structure and expression profile of Dok-3 and highlight its role during signal transduction in B cells, innate cells as well as in bone and lung tissues.
Highlights
The specific response of cells to environmental stimuli requires crosstalk between multiple signaling pathways, and such specificity in signaling is achieved through a class of proteins known as adaptors, which link specific protein partners together, in a reversible manner, via their protein binding modules to elicit the appropriate cellular response [1]
Since Downstream of kinase (Dok)-3 has the tendency to interact with these two inhibitory molecules upon engagement of B cell-receptor (BCR), and overexpression of Dok-3 inhibited BCR-mediated nuclear factor of activated T-cells (NFAT) activation and Interleukin (IL)2 secretion in stimulated B cells, this study provided the first line of evidence that Dok-3 functions as a negative regulator of immunoreceptor signaling in B cells [8] (Figure 3A)
Downstream of kinase 3 belongs to the Dok family of adaptor proteins, and it has some degree of homology, and as such overlapping functions, with other Dok members, in particular Dok-1 and -2
Summary
The specific response of cells to environmental stimuli requires crosstalk between multiple signaling pathways, and such specificity in signaling is achieved through a class of proteins known as adaptors, which link specific protein partners together, in a reversible manner, via their protein binding modules to elicit the appropriate cellular response [1]. As the roles of Dok-3 in different cell types are starting to be unraveled, accumulating evidence suggests that Dok-3 can function, in a context-dependent manner, as both a positive and negative regulator of signaling pathways, in both immune as well as non-immune cells (Figure 3 and Table 1).
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