High impact information on DOK2

• T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2 [1].
• Further studies revealed that the change in mobility of Dok-2 was brought about by tyrosine phosphorylation [2].
• Phosphotyrosine binding-mediated oligomerization of downstream of tyrosine kinase (Dok)-1 and Dok-2 is involved in CD2-induced Dok phosphorylation [3].
• In T cells, two members, Dok-1 and Dok-2, are expressed [3].
• We showed that the Dok PTB domain mediates phosphotyrosine-dependent homotypic and heterotypic interactions of Dok-1 and Dok-2 [3].

Biological context of DOK2

• p62(DOK1) (DOK1) and p56(DOK2) (DOK2) are sequence homologs that act as docking proteins downstream of receptor or nonreceptor tyrosine kinases [4].
• The data provide evidence that DOK1 and DOK2 proteins have a similar role in regulating cell proliferation and differentiation and are positive regulators of the MAPK signaling pathway in this context [4].

Anatomical context of DOK2

• The data in this report show that both the DOK1 and the DOK2 adaptor proteins are constitutively expressed in the myelomonoblastic leukemia cell line, HL-60, and that expression of both proteins is induced by the chemotherapeutic differentiation causing agents, all-trans retinoic acid (atRA) and 1,25-dihydroxyvitamin D3 (VD3) [4].
• Moreover, in CD2-stimulated Jurkat cells, Dok-1 coimmunoprecipitates with tyrosine-phosphorylated Dok-2 [3].

Associations of DOK2 with chemical compounds

• Dok-R, also known as Dok-2/FRIP, belongs to the DOK family of signaling molecules that become tyrosine-phosphorylated by several different receptor and cytoplasmic tyrosine kinases [5].
• Further, they raise the interesting possibility that Dok2 plays an important role in integrin outside-in signaling through a physical and functional interaction with integrin alpha(IIb)beta(3) [6].
• Background: We previously demonstrated that Dok2 is rapidly phosphorylated on tyrosine residues in platelets in response to thrombin, the immunoreceptor tyrosine-based activation motif-coupled collagen receptor glycoprotein (GP) VI, and by integrin alpha(IIb)beta(3) [6].

Other interactions of DOK2

• Dok-1, Dok-2 and Dok-3 comprise a closely related family of adaptor, which negatively regulates mitogen-activated protein kinase Erk downstream of protein-tyrosine kinases (PTKs) [7].

Analytical, diagnostic and therapeutic context of DOK2

• Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins [8].

References