Dock180

Dock180
Dedicator of cytokinesis 1
Identifiers
Symbols DOCK1; DOCK180; ced5
External IDs OMIM601403 MGI2429765 HomoloGene55575 GeneCards: DOCK1 Gene
Orthologs
Species Human Mouse
Entrez 1793 330662
Ensembl ENSG00000150760 ENSMUSG00000058325
UniProt Q14185 Q8BUR4
RefSeq (mRNA) NM_001380 NM_001033420.2
RefSeq (protein) NP_001371 NP_001028592.1
Location (UCSC) Chr 10:
128.59 – 129.25 Mb
Chr 7:
141.86 – 142.37 Mb
PubMed search [1] [2]

Dock180, (Dedicator of cytokinesis) also known as DOCK1, is a large (~180 kDa) protein involved in intracellular signalling networks.[1] It is the mammalian ortholog of the C. elegans protein CED-5 and belongs to the DOCK family of Guanine nucleotide exchange factors (GEFs).[2]

Contents

Discovery

Dock180 was identified, using a far-western blotting approach, as a binding partner of the adaptor protein Crk that was able to induce morphological changes in 3T3 fibroblasts.[3] Subsequently it was reported that Dock180 was able to activate the small GTP-binding protein (G protein) Rac1[4] and this was later shown to happen via its ability to act as a GEF.[5]

Structure and Function

Dock180 is part of a large class of proteins (GEFs) which contibrute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting this nucleotide exchange.

Dock180 and related proteins differ from other GEFs in that they do not possess the canonical structure of tandem DH-PH domains known to elicit nucleotide exchange. Instead they possess a DHR2 domain which mediates Rac activation by stabilising it in its nucleotide-free state.[5] Dock180-related proteins also possess a DHR1 domain which has been shown, in vitro, to bind phospholipids[6] and which may be involved in their interaction with cellular membranes. Other structural features of Dock180 include an N-terminal SH3 domain involved in binding to ELMO proteins (see below)[7] and a C-terminal proline-rich region which, in Myoblast city (the Drosophila melanogaster ortholog of Dock180), was shown to bind DCrk (the Drosophila ortholog of Crk).[8]

Regulation of Dock180 Activity

Under physiological conditions Dock180 alone is inefficient at promoting nucleotide exchange on Rac.[7] Effective GEF activity requires an interaction between Dock180 and its binding partner ELMO. ELMO1 is the most comprehensively described isoform of this small family of non-catalytically active proteins which function to recruit Dock180 to the plasma membrane and induce conformational changes which increase GEF efficiency.[9][10][11] ELMO1 has also been reported to inhibit ubiqitinylation of Dock180 and so prevent its degradation by proteasomes.[12] Receptor-mediated activation of RhoG (a small G protein of the Rac subfamily) is perhaps the best known inducer of Dock180 GEF activity. Active (GTP-bound) RhoG recruits the ELMO/Dock180 complex to the plasma membrane thereby bringing Dock180 into contact with its substrate, Rac.[13] In tumour cells Dock180 is regulated by a complex containing Crk and p130Cas which is in turn regulated by cooperative signalling by β3-containing integrin complexes and the membrane-bound protein uPAR.[14]

Signalling Downstream of Dock180

Dock180 is a Rac-specific GEF and so is responsible for a subset of Rac-specific signalling events. These include cell migration and phagocytosis of apoptotic cells in C. elegans,[15] neurite outgrowth in PC12 cells[16] and myoblast fusion in the Zebrafish embryo.[17] More recently the DHR1 domain of Dock180 was shown to bind SNX5 (a sorting nexin) and this interaction promoted retrograde transport of the cation-independent mannose 6-phosphate receptor to the Trans-Golgi Network in a Rac-independent manner.[18] Increased expression of Dock180 and Elmo has been reported to contribute to glioma invasion.[19]

Interactions

Dock180 has been shown to interact with BCAR1,[20] Grb2,[20][21] CRK[20][21][22][23][24] and ELMO1.[25][26]

References

  1. ^ "Entrez Gene: DOCK1 dedicator of cytokinesis 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1793. 
  2. ^ Meller N, Merlot S, Guda C (November 2005). "CZH proteins: a new family of Rho-GEFs". J. Cell Sci. 118 (Pt 21): 4937–46. doi:10.1242/jcs.02671. PMID 16254241. 
  3. ^ Hasegawa H, Kiyokawa E, Tanaka S, et al. (April 1996). "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane". Mol. Cell. Biol. 16 (4): 1770–76. PMC 231163. PMID 8657152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231163. 
  4. ^ Kiyokawa E, Hashimoto Y, Kobayashi S, et al. (November 1998). "Activation of Rac1 by a Crk SH3-binding protein, DOCK180". Genes Dev. 12 (21): 3331–36. doi:10.1101/gad.12.21.3331. PMC 317231. PMID 9808620. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317231. 
  5. ^ a b Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". J. Cell Sci. 115 (Pt 24): 4901–13. doi:10.1242/jcs.00219. PMID 12432077. 
  6. ^ Côté JF, Motoyama AB, Bush JA, et al. (August 2005). "A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signalling". Nat. Cell Biol. 7 (8): 797–807. doi:10.1038/ncb1280. PMC 1352170. PMID 16025104. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1352170. 
  7. ^ a b Brugnera E, Haney L, Grimsley C, et al. (August 2002). "Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex". Nat. Cell Biol. 4 (8): 574–82. doi:10.1038/ncb824. PMID 12134158. 
  8. ^ Balagopalan L, Chen MH, Geisbrecht ER, et al. (December 2006). "The CDM superfamily protein MBC directs myoblast fusion through a mechanism that requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of direct interaction with DCrk". Mol. Cell. Biol. 26 (24): 9442–55. doi:10.1128/MCB.00016-06. PMC 1698515. PMID 17030600. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1698515. 
  9. ^ Lu M, Ravichandran KS (2006). "Dock180-ELMO cooperation in Rac activation". Meth. Enzym. 406: 388–402. doi:10.1016/S0076-6879(06)06028-9. PMID 16472672. 
  10. ^ Lu M, Kinchen JM, Rossman KL, et al. (2004). "PH domain of ELMO functions in trans to regulate Rac activation via Dock180". Nat. Struc. Mol. Biol. 11 (8): 756–62. doi:10.1038/nsmb800. PMID 15247908. 
  11. ^ Lu M, Kinchen JM, Rossman KL, et al. (February 2005). "A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs". Curr. Biol. 15 (4): 371–77. doi:10.1016/j.cub.2005.01.050. PMID 15723800. 
  12. ^ Makino Y, Tsuda M, Ichihara S, et al. (March 2006). "Elmo1 inhibits ubiquitylation of Dock180". J. Cell Sci. 119 (Pt 5): 923–32. doi:10.1242/jcs.02797. PMID 16495483. 
  13. ^ Katoh H, Negishi M (July 2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature 424 (6947): 461–64. doi:10.1038/nature01817. PMID 12879077. 
  14. ^ Smith HW, Marra P, Marshall CJ (August 2008). "uPAR promotes formation of the p130Cas-Crk complex to activate Rac through DOCK180". J. Cell Biol. 182 (4): 777–90. doi:10.1083/jcb.200712050. PMC 2518715. PMID 18725541. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2518715. 
  15. ^ Gumienny TL, Brugnera E, Tosello-Trampont AC, et al. (October 2001). "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration". Cell 107 (1): 27–41. doi:10.1016/S0092-8674(01)00520-7. PMID 11595183. 
  16. ^ Katoh H, Yasui H, Yamaguchi Y, et al. (October 2000). "Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells". Mol. Cell. Biol. 20 (19): 7378–87. doi:10.1128/MCB.20.19.7378-7387.2000. PMC 86291. PMID 10982854. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86291. 
  17. ^ Moore CA, Parkin CA, Bidet Y, et al. (September 2007). "A role for the Myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion". Development 134 (17): 3145–53. doi:10.1242/dev.001214. PMID 17670792. 
  18. ^ Hara S, Kiyokawa E, Iemura SI, et al. (July 2008). "The DHR1 Domain of DOCK180 Binds to SNX5 and Regulates Cation-independent Mannose 6-phosphate Receptor Transport". Mol. Biol. Cell (article in press) (9): 3823–35. doi:10.1091/mbc.E08-03-0314. PMC 2526700. PMID 18596235. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2526700. 
  19. ^ Jarzynka MJ, Hu B, Hui KM, et al. (August 2007). "ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion". Cancer Res. 67 (15): 7203–11. doi:10.1158/0008-5472.CAN-07-0473. PMC 2867339. PMID 17671188. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2867339. 
  20. ^ a b c Hsia, Datsun A; Mitra Satyajit K, Hauck Christof R, Streblow Daniel N, Nelson Jay A, Ilic Dusko, Huang Shuang, Li Erguang, Nemerow Glen R, Leng Jay, Spencer Kathryn S R, Cheresh David A, Schlaepfer David D (Mar. 2003). "Differential regulation of cell motility and invasion by FAK". J. Cell Biol. (United States) 160 (5): 753–67. doi:10.1083/jcb.200212114. ISSN 0021-9525. PMC 2173366. PMID 12615911. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173366. 
  21. ^ a b Hasegawa, H; Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M, Kurata T, Matsuda M (Apr. 1996). "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane". Mol. Cell. Biol. (UNITED STATES) 16 (4): 1770–6. ISSN 0270-7306. PMC 231163. PMID 8657152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231163. 
  22. ^ Nishihara, H; Kobayashi S, Hashimoto Y, Ohba F, Mochizuki N, Kurata T, Nagashima K, Matsuda M (Nov. 1999). "Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins". Biochim. Biophys. Acta (NETHERLANDS) 1452 (2): 179–87. doi:10.1016/S0167-4889(99)00133-0. ISSN 0006-3002. PMID 10559471. 
  23. ^ Gu, J; Sumida Y, Sanzen N, Sekiguchi K (Jul. 2001). "Laminin-10/11 and fibronectin differentially regulate integrin-dependent Rho and Rac activation via p130(Cas)-CrkII-DOCK180 pathway". J. Biol. Chem. (United States) 276 (29): 27090–7. doi:10.1074/jbc.M102284200. ISSN 0021-9258. PMID 11369773. 
  24. ^ Matsuda, M; Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T (Jun. 1996). "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins". J. Biol. Chem. (UNITED STATES) 271 (24): 14468–72. doi:10.1074/jbc.271.24.14468. ISSN 0021-9258. PMID 8662907. 
  25. ^ Gumienny, T L; Brugnera E, Tosello-Trampont A C, Kinchen J M, Haney L B, Nishiwaki K, Walk S F, Nemergut M E, Macara I G, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner M O, Ravichandran K S (Oct. 2001). "CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration". Cell (United States) 107 (1): 27–41. doi:10.1016/S0092-8674(01)00520-7. ISSN 0092-8674. PMID 11595183. 
  26. ^ Brugnera, Enrico; Haney Lisa, Grimsley Cynthia, Lu Mingjian, Walk Scott F, Tosello-Trampont Annie-Carole, Macara Ian G, Madhani Hiten, Fink Gerald R, Ravichandran Kodimangalam S (Aug. 2002). "Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex". Nat. Cell Biol. (England) 4 (8): 574–82. doi:10.1038/ncb824. ISSN 1465-7392. PMID 12134158. 

Further reading

External links



Wikimedia Foundation. 2010.

Игры ⚽ Нужно решить контрольную?

Look at other dictionaries:

  • Dock2 — Dedicator of cytokinesis 2 Rendering based on PDB 2RQR …   Wikipedia

  • RhoG — (Ras homology Growth related) (or ARGH) is a small ( 21 kDa) monomeric GTP binding protein (G protein), and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G… …   Wikipedia

  • Dock4 — Dedicator of cytokinesis 4 Identifiers Symbols DOCK4; FLJ34238; KIAA0716; MGC134911; MGC134912 External IDs …   Wikipedia

  • Dock3 — Dedicator of cytokinesis 3 Identifiers Symbols DOCK3; KIAA0299; MOCA; PBP External IDs …   Wikipedia

  • ELMO1 — Engulfment and cell motility 1, also known as ELMO1, is a human gene.cite web | title = Entrez Gene: ELMO1 engulfment and cell motility 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=9844| accessdate = ] …   Wikipedia

  • ELMO (protein) — Pfam box Symbol = ELMO CED12 Name = ELMO/CED 12 family Pfam= PF04727 InterPro= IPR006816 SMART= PROSITE = PDOC51335 SCOP = TCDB = PDB = ELMO (Engulfment and Cell Motility) is a family of related proteins ( 82 kDa) involved in intracellular… …   Wikipedia

  • Dock5 — Dedicator of cytokinesis 5 Identifiers Symbols DOCK5; DKFZp451J181; DKFZp779M164; DKFZp781J211 External IDs …   Wikipedia

  • Dock6 — Dedicator of cytokinesis 6 Identifiers Symbols DOCK6; ZIR1 External IDs MGI:&# …   Wikipedia

  • Dock7 — Dedicator of cytokinesis 7 Identifiers Symbols DOCK7; KIAA1771; ZIR2 External IDs …   Wikipedia

  • Dock8 — Dedicator of cytokinesis 8 Identifiers Symbols DOCK8; FLJ00026; FLJ00152; FLJ00346; MRD2; ZIR8 External IDs …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”