The downstream of kinase family (Dok-1-7) are members of a class of “docking” proteins that include the tyrosine kinase substrates IRS-1 and Cas, which contain multiple tyrosine residues and putative SH2 binding sites. Dok-4, Dok-5 and Dok-6 are more similar to each other than to the other Dok family members, and may constitute a subfamily of the DOK genes. Dok-5 is a tyrosine kinase substrate that enhances c-Ret-dependent activation of mitogen-activated protein kinase (MAPK). Dok-5 transcript is abundant in muscle and increases during T cell activation. Dok-5 protein undergoes tyrosine phosphorylation in response to insulin and insulin-like growth factor-1. Dok-6 is highly expressed in the developing central nervous system. It associates with Ret to transduce Ret-mediated processes such as axonal projection.
Function:
DOK6 (docking protein 6) is a novel member of the DOK4/5 subclass of the p62 DOK family of intracellular adaptor molecules. DOK6 is highly expressed in the developing central nervous system and is co expressed with Ret in several locations, including sympathetic, sensory, and parasympathetic ganglia, as well as in the ureteric buds of the developing kidneys. Pull down assays using the DOK6 phosphotyrosine binding (PTB) domain and GDNF activated Ret indicate that DOK6 binds to the phosphorylated Ret Tyr(1062) residue. Moreover, ligand activation of Ret resulted in phosphorylation of tyrosine residue(s) located within the unique C terminus of DOK6 predominantly through a Src dependent mechanism, indicating that DOK6 is a substrate of the Ret Src signaling pathway.
Subunit:
Interacts via its PTB domain with phosphorylated RET.
Tissue Specificity:
Highly expressed in fetal and adult brain. Highly expressed in the cerebellum. Weak expression in kidney, spinal cord and testis.
Post-translational modifications:
On Ret activation, phosphorylated on one or more SLCterminal tyrosine residues by an Src family kinase.
Similarity:
Belongs to the DOK family. Type B subfamily.
Contains 1 IRS-type PTB domain.
Contains 1 PH domain.
SWISS:
Q6PKX4
Gene ID:
220164
Database links:
Entrez Gene: 220164 Human
Entrez Gene: 623279 Mouse
Omim: 611402 Human
SwissProt: Q6PKX4 Human
SwissProt: Q2MHE5 Mouse
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