DOK2 explained

Docking protein 2 is a protein that in humans is encoded by the DOK2 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells.^[3]

Interactions

DOK2 has been shown to interact with INPP5D^[4] and TEK tyrosine kinase.^{[5] [6]}

Further reading

• Jiang H, Harris MB, Rothman P . IL-4/IL-13 signaling beyond JAK/STAT. . J. Allergy Clin. Immunol. . 105 . 6 Pt 1 . 1063–70 . 2000 . 10856136 . 10.1067/mai.2000.107604 . free .
• Jones N, Dumont DJ . The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R. . Oncogene . 17 . 9 . 1097–108 . 1998 . 9764820 . 10.1038/sj.onc.1202115 . 20187169 .
• Jones N, Dumont DJ . Recruitment of Dok-R to the EGF receptor through its PTB domain is required for attenuation of Erk MAP kinase activation. . Curr. Biol. . 9 . 18 . 1057–60 . 2000 . 10508618 . 10.1016/S0960-9822(99)80458-8 . 18831513 . free .
• Némorin JG, Duplay P . Evidence that Llck-mediated phosphorylation of p56dok and p62dok may play a role in CD2 signaling. . J. Biol. Chem. . 275 . 19 . 14590–7 . 2000 . 10799545 . 10.1074/jbc.275.19.14590 . free .
• Dunant NM, Wisniewski D, Strife A . The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells. . Cell. Signal. . 12 . 5 . 317–26 . 2000 . 10822173 . 10.1016/S0898-6568(00)00073-5 . etal.
• Némorin JG, Laporte P, Bérubé G, Duplay P . p62dok negatively regulates CD2 signaling in Jurkat cells. . J. Immunol. . 166 . 7 . 4408–15 . 2001 . 11254695 . 10.4049/jimmunol.166.7.4408. free .
• Grimm J, Sachs M, Britsch S . Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation. . J. Cell Biol. . 154 . 2 . 345–54 . 2001 . 11470823 . 10.1083/jcb.200102032 . 2150770 . etal.
• Master Z, Jones N, Tran J . Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak. . EMBO J. . 20 . 21 . 5919–28 . 2001 . 11689432 . 10.1093/emboj/20.21.5919 . 125712 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Salomon AR, Ficarro SB, Brill LM . Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. . Proc. Natl. Acad. Sci. U.S.A. . 100 . 2 . 443–8 . 2003 . 12522270 . 10.1073/pnas.2436191100 . 141014 . 2003PNAS..100..443S . etal. free .
• Jones N, Chen SH, Sturk C . A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function. . Mol. Cell. Biol. . 23 . 8 . 2658–68 . 2003 . 12665569 . 10.1128/MCB.23.8.2658-2668.2003 . 152553 . etal.
• Master Z, Tran J, Bishnoi A . Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization. . J. Biol. Chem. . 278 . 32 . 30170–9 . 2003 . 12777393 . 10.1074/jbc.M301339200 . etal. free .
• Gérard A, Favre C, Garçon F . Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase. . Oncogene . 23 . 8 . 1594–8 . 2004 . 14647425 . 10.1038/sj.onc.1207283 . 11822165 . etal.
• Brill LM, Salomon AR, Ficarro SB . Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. . Anal. Chem. . 76 . 10 . 2763–72 . 2004 . 15144186 . 10.1021/ac035352d . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Rush J, Moritz A, Lee KA . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. . Nat. Biotechnol. . 23 . 1 . 94–101 . 2005 . 15592455 . 10.1038/nbt1046 . 7200157 . etal.
• Van Slyke P, Coll ML, Master Z . Dok-R mediates attenuation of epidermal growth factor-dependent mitogen-activated protein kinase and Akt activation through processive recruitment of c-Src and Csk. . Mol. Cell. Biol. . 25 . 9 . 3831–41 . 2005 . 15831486 . 10.1128/MCB.25.9.3831-3841.2005 . 1084282 . etal.

Notes and References

1. Di Cristofano A, Carpino N, Dunant N, Friedland G, Kobayashi R, Strife A, Wisniewski D, Clarkson B, Pandolfi PP, Resh MD . Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins . J Biol Chem . 273 . 9 . 4827–30 . March 1998 . 9478921 . 10.1074/jbc.273.9.4827 . free .
2. Garcia A, Prabhakar S, Hughan S, Anderson TW, Brock CJ, Pearce AC, Dwek RA, Watson SP, Hebestreit HF, Zitzmann N . Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins . Blood . 103 . 6 . 2088–95 . March 2004 . 14645010 . 10.1182/blood-2003-07-2392 . free .
3. Web site: Entrez Gene: DOK2 docking protein 2, 56kDa.
4. Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD . The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells . Cell. Signal. . 12 . 5 . 317–26 . 2000 . 10822173 . 10.1016/S0898-6568(00)00073-5 .
5. Jones N, Dumont DJ . The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R . Oncogene . 17 . 9 . 1097–108 . 1998 . 9764820 . 10.1038/sj.onc.1202115 . 20187169 .
6. Master Z, Jones N, Tran J, Jones J, Kerbel RS, Dumont DJ . Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak . EMBO J. . 20 . 21 . 5919–28 . 2001 . 11689432 . 125712 . 10.1093/emboj/20.21.5919 .