High impact information on Dok1

• We have recently shown that protein tyrosine phosphatase 1B (PTP1B) associates with the docking protein p130Cas in 3Y1 rat fibroblasts [1].
• The Crk-associated substrate (Cas) is a unique docking protein that possesses a repetitive stretch of tyrosine-containing motifs and an Src homology 3 (SH3) domain [2].
• Insulin receptor substrate-1 (IRS-1) is a multisite docking protein occupying a central position in signaling cascades stimulated by a number of growth factors including insulin [3].
• We conclude that Shc serves as a primary docking protein for GRB2 in smooth muscle cells and is critical for proliferation in response to PDGF [4].
• Dexamethasone up-regulates the inhibitory adaptor protein Dok-1 and suppresses downstream activation of the mitogen-activated protein kinase pathway in antigen-stimulated RBL-2H3 mast cells [5].

Biological context of Dok1

• Hence Dok-1/Dok-2 may also be involved in the FcepsilonRI-stimulated processes of cytoskeleton rearrangement required for cell adhesion, membrane ruffling and exocytosis [6].
• None of these agents increased the phosphorylation of the EGFR or the docking protein Shc [7].

Anatomical context of Dok1

• On the basis of these results it is concluded that docking protein is a functionally characterized integral protein specifically restricted to rough microsomal membranes [8].
• Whereas a number of proteins, including cytochromes b5 and P-450 and their reductases were evenly distributed between rough and smooth microsomes, docking protein was found at 20-fold higher levels in the rough fraction [8].
• Docking protein (or SRP receptor) is an integral membrane protein essential for translocation of nascent polypeptides across the membrane of the endoplasmic reticulum (ER) [9].
• Restriction of docking protein to the rough endoplasmic reticulum: immunocytochemical localization in rat liver [9].
• Quantitative evaluation of labeling suggests that there is one molecule of docking protein for roughly 10 to 20 bound ribosomes [9].

Associations of Dok1 with chemical compounds

• These findings identify Dok-1 as mediator of the antiallergic actions of dexamethasone and as a negative regulator of the MAP kinase pathway and downstream release of inflammatory mediators [5].
• The negative regulatory role of Dok-1 was further validated by the expression of small interfering RNA directed against Dok-1, which enhanced activation of MAP kinase and subsequent release of arachidonic acid and tumor necrosis factor-alpha [5].

Enzymatic interactions of Dok1

• The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation [10].

Other interactions of Dok1

• The same effects were obtained by transient overexpression of Dok-1 but not by overexpression of Dok-1 that was mutated in RasGAP-binding domain [5].
• Insulin receptor-substrate-1 (IRS-1) is a docking protein for several tyrosine kinase receptors [11].

References