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.