Cytokine Receptor-like Factor 3 (CRLF3) and Its Emerging Roles in Neurobiology, Hematopoiesis and Related Human...

Cytokine receptor-like factor 3 (CRLF3) has an extended evolutionary history, which has been conserved across metazoan species. It consists of several structural elements, notably including a fibronectin type 3 (FBNIII) domain containing a WSXWS motif that is synonymous with so-called class I cytokine receptors present throughout bilaterial species, and a proposed spl1 and ryanodine receptor (SPRY) domain that represents a widespread protein-protein interaction module. The function of CRLF3 has remained enigmatic, but several recent investigations have revealed critical insights into its biological roles. These studies suggest that CRLF3 principally functions in neural and hematopoietic cells, where it plays critical and diverse roles in the development and function of specific cell populations. Disruption of CRLF3 has also been associated with several human diseases, mainly associated with these same lineages but also including malignancy. The mechanisms by which CRLF3 exerts these diverse effects remain uncertain, although a number of potential options have emerged.