Dedicator of cytokinesis protein 8: Difference between revisions
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Despite the fact that little is known about the cellular role of Dock8 its importance has been highlighted in several studies which have identified distruption of the ''DOCK8'' gene in disease. [[Deletion (genetics)|Deletion]] and reduced [[gene expression|expression]] of Dock8 have been reported in a human [[lung cancer]] cell line<ref name="Takahashi_2006">{{cite journal | author = Takahashi K, Kohno T, Ajima R, ''et al.''| title = Homozygous deletion and reduced expression of the DOCK8 gene in human lung cancer| journal = Int. J. Oncol. | volume = 28 | issue = 2 | pages = 321–28| year = 2006 | month = February| pmid = 16391785 | doi = | url = | issn = }}</ref> and Dock8 was also identified as a putative candidate gene associated with progression of [[glioma]]s.<ref name="Idbaih_2008">{{cite journal | author = Idbaih A, Carvalho Silva R, Crinière E, ''et al.''| title = Genomic changes in progression of low-grade gliomas| journal =J. Neurooncol. | volume = Article in press | issue = | pages = | year = 2008 | month = July| pmid = 18618226 | doi = | url = | issn = }}</ref> Interestingly, Dock8 has been reported to be disrupted in two unrelated patients with [[mental retardation]].<ref name="Griggs_2008">{{cite journal | author = Griggs BL, Ladd S, Saul RA, ''et al.''| title = Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities| journal =Genomics | volume = 91 | issue = 2| pages = 195| year = 2008 | month = February| pmid = 18060736 | doi = 10.1016/j.ygeno.2007.10.011| url = }}</ref> |
Despite the fact that little is known about the cellular role of Dock8 its importance has been highlighted in several studies which have identified distruption of the ''DOCK8'' gene in disease. [[Deletion (genetics)|Deletion]] and reduced [[gene expression|expression]] of Dock8 have been reported in a human [[lung cancer]] cell line<ref name="Takahashi_2006">{{cite journal | author = Takahashi K, Kohno T, Ajima R, ''et al.''| title = Homozygous deletion and reduced expression of the DOCK8 gene in human lung cancer| journal = Int. J. Oncol. | volume = 28 | issue = 2 | pages = 321–28| year = 2006 | month = February| pmid = 16391785 | doi = | url = | issn = }}</ref> and Dock8 was also identified as a putative candidate gene associated with progression of [[glioma]]s.<ref name="Idbaih_2008">{{cite journal | author = Idbaih A, Carvalho Silva R, Crinière E, ''et al.''| title = Genomic changes in progression of low-grade gliomas| journal =J. Neurooncol. | volume = Article in press | issue = | pages = | year = 2008 | month = July| pmid = 18618226 | doi = | url = | issn = }}</ref> Interestingly, Dock8 has been reported to be disrupted in two unrelated patients with [[mental retardation]].<ref name="Griggs_2008">{{cite journal | author = Griggs BL, Ladd S, Saul RA, ''et al.''| title = Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities| journal =Genomics | volume = 91 | issue = 2| pages = 195| year = 2008 | month = February| pmid = 18060736 | doi = 10.1016/j.ygeno.2007.10.011| url = }}</ref> |
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Autosomal recessive DOCK8 deficiency is associated with a variant of [[combined immunodeficiency]]. Persons with an previously unknown variant of [[Hyperimmunoglobulin E syndrome]] (HIES) were found to have a genetic mutation |
Autosomal recessive DOCK8 deficiency is associated with a variant of [[combined immunodeficiency]]. Persons with an previously unknown variant of [[Hyperimmunoglobulin E syndrome]] (HIES) were found to have a genetic mutation in the Dock8 gene.<ref name="pmid19776401">{{cite journal | author = Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, Matthews HF, Davis J, Turner ML, Uzel G, Holland SM, Su HC | title = Combined Immunodeficiency Associated with DOCK8 Mutations | journal = N. Engl. J. Med. | volume = | issue = | pages = | year = 2009 | month = September | pmid = 19776401 | doi = 10.1056/NEJMoa0905506 | url = | laysummary = http://www.nih.gov/news/health/sep2009/niaid-24.htm | laysource = nih.gov/news }}</ref> |
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==References== |
==References== |
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Revision as of 19:04, 28 September 2009
Template:PBB Dock8 (Dedicator of cytokinesis 8), also known as Zir3, is a large (~190 kDa) protein involved in intracellular signalling networks.[1] It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins.
Discovery
Dock8 was identified during a yeast two hybrid (YTH) screen for proteins that interact with the Rho family small G protein Cdc42.[2] Subsequent northern blot analysis revealed high levels of Dock8 expression in the placenta, lung, kidney and pancreas as well as lower levels in the heart, brain and skeletal muscle.
Function
Dock8 shares the same core domain arrangement as all other DOCK proteins, with a DHR2 domain which, in other proteins, contains GEF activity and a DHR1 domain known, in other proteins, to interact with phospholipids. In the YTH system Dock8 was reported to interact with both Rac1 and Cdc42. However, no stable interaction between Dock8 and these small G proteins was observed in a GST-pulldown assay. This may be due to the fact many DOCK-G protein interactions require the presence of adaptor proteins to stabilise the complex and thus facilitate nucleotide exchange.[3]
Dock8 in disease
Despite the fact that little is known about the cellular role of Dock8 its importance has been highlighted in several studies which have identified distruption of the DOCK8 gene in disease. Deletion and reduced expression of Dock8 have been reported in a human lung cancer cell line[4] and Dock8 was also identified as a putative candidate gene associated with progression of gliomas.[5] Interestingly, Dock8 has been reported to be disrupted in two unrelated patients with mental retardation.[6]
Autosomal recessive DOCK8 deficiency is associated with a variant of combined immunodeficiency. Persons with an previously unknown variant of Hyperimmunoglobulin E syndrome (HIES) were found to have a genetic mutation in the Dock8 gene.[7]
References
- ^ "Entrez Gene: DOCK8 dedicator of cytokinesis 8".
- ^ Ruusala A, Aspenström P (2004). "Isolation and characterisation of DOCK8, a member of the DOCK180-related regulators of cell morphology". FEBS Letters. 572 (1–3): 159–66. doi:10.1016/j.febslet.2004.06.095. PMID 15304341.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Lu M, Ravichandran KS (2006). "Dock180-ELMO cooperation in Rac activation". Methods Enzymol. 406: 388–402. doi:10.1016/S0076-6879(06)06028-9. PMID 16472672.
{{cite journal}}: Cite has empty unknown parameter:|month=(help) - ^ Takahashi K, Kohno T, Ajima R; et al. (2006). "Homozygous deletion and reduced expression of the DOCK8 gene in human lung cancer". Int. J. Oncol. 28 (2): 321–28. PMID 16391785.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Idbaih A, Carvalho Silva R, Crinière E; et al. (2008). "Genomic changes in progression of low-grade gliomas". J. Neurooncol. Article in press. PMID 18618226.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Griggs BL, Ladd S, Saul RA; et al. (2008). "Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities". Genomics. 91 (2): 195. doi:10.1016/j.ygeno.2007.10.011. PMID 18060736.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, Matthews HF, Davis J, Turner ML, Uzel G, Holland SM, Su HC (2009). "Combined Immunodeficiency Associated with DOCK8 Mutations". N. Engl. J. Med. doi:10.1056/NEJMoa0905506. PMID 19776401.
{{cite journal}}: Unknown parameter|laysource=ignored (help); Unknown parameter|laysummary=ignored (help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
Further reading
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