Background

Dedicator of Cytokinesis 8 (DOCK8) is a protein that regulates the actin cytoskeleton, with particular importance in immune cells and a key role in innate and adaptive immune responses.

 What is the molecular weight of DOCK8?

231 kDa. DOCK8 is a protein composed of 2031 amino acids and is a guanine nucleotide exchange factor (GEF).

 What is the function of DOCK8?

DOCK8 is a member of the DOCK family of proteins, which have a unique DRH2 domain enabling them to act as GEFs and so controlling a range of cellular processes in various signaling pathways (PMID: 12432077). The specific target of DOCK8 is Cell division control protein 42 homolog (Cdc42), a small GTPase that is involved in regulation of the cell cycle and forms a complex. DOCK8 also acts as a scaffold molecule in this complex that initiates actin polymerization via the Wiskott-Aldrich Syndrome protein (WASp) (PubMed: 28028151, PubMed: 22461490).

 What diseases are associated with DOCK8?

The role of DOCK8 in immunity was first identified with the study of DOCK8-deficient patients who presented with combined immunodeficiency (PMID: 19776401; PMID: 20004785). The subsequent study of DOCK8 in immune cells such as T cells, natural killer (NK) cells, and B cells has revealed how it regulates their normal function. This includes the regulation of immune synapse formation, immune cell trafficking, regulation of dendritic cell polarization, and cytokine production (PMID: 28366940).

DOCK8 deficiency is caused by a number of different mutations in the gene. It leads to the autosomal recessive form of the immunodeficiency disease Hyper-IgE syndrome, or Job's syndrome. The symptoms of DOCK8 deficiency include eczema, high levels of serum IgE, hypereosinophilia, and recurrent respiratory and skin infections as a result of impaired immune cell function.