Dok Family Proteins in Cancer Biology

Dok (downstream of kinase) proteins constitute a family of non-enzymatic adaptor molecules distinguished by an N-terminal pleckstrin homology (PH) domain and a central phosphotyrosine-binding (PTB) domain. By serving as molecular scaffolds, these proteins coordinate signalling complexes downstream of receptor and non-receptor tyrosine kinases, thereby modulating pathways such as RAS/MAPK, PI3K/AKT and JAK/STAT. In cancer contexts, distinct Dok members may function as tumour suppressors, restraining proliferative and migratory signals, or as tumoral modulators influencing the microenvironment and immune surveillance. Genomic alterations, including chromosomal breaks and reduced expression at fragile sites, can impair Dok-mediated feedback loops and promote oncogenic signalling. Aberrant splicing and post-translational modifications further diversify Dok activities, with emerging evidence implicating these proteins in tumour progression, metastasis and therapeutic resistance. Their central position in signal transduction renders Dok adaptors promising diagnostic markers and attractive targets for novel anticancer interventions.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Dok Family Proteins in Cancer Biology publication trend

The graph below shows the total number of articles in dok family proteins in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Adaptor protein: A non-enzymatic molecule that organises signalling complexes by binding to multiple partners via specialised domains.

Pleckstrin homology (PH) domain: A protein module that binds phosphoinositide lipids, mediating recruitment to cell membranes.

Phosphotyrosine-binding (PTB) domain: A domain that recognises phosphorylated tyrosine residues within partner proteins, facilitating signal transduction.

Common fragile site: A chromosomal region prone to breakage under replication stress, often associated with tumour suppressor gene disruption.

RAS/MAPK pathway: A cascade of kinases transmitting signals from cell-surface receptors to the nucleus, regulating proliferation and differentiation.

References

1. Chromosomal breaks at FRA18C: association with reduced DOK6 expression, altered oncogenic signaling and increased gastric cancer survival. npj Precision Oncology (2017).
2. DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma. PLOS ONE (2013).
3. The downstream of tyrosine kinase 7 is reduced in lung cancer and is associated with poor survival of patients with lung cancer. Oncology Reports (2017).