View source for MAP4K2

{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
'''Mitogen-activated protein kinase kinase kinase kinase 2''' is an [[enzyme]] that in humans is encoded by the ''MAP4K2'' [[gene]].<ref name="pmid7515885">{{cite journal | vauthors = Katz P, Whalen G, Kehrl JH | title = Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center | journal = The Journal of Biological Chemistry | volume = 269 | issue = 24 | pages = 16802–9 | date = Jun 1994 | doi = 10.1016/S0021-9258(19)89463-2 | pmid = 7515885 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MAP4K2 mitogen-activated protein kinase kinase kinase kinase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5871}}</ref>
== Function ==
The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1.<ref name="entrez"/> A recent study showed that MAP4K2 is a direct kinase of LATS1/2 and thus regulates the Hippo pathway effectors YAP and TAZ.<ref>{{Cite journal
| last1 = Meng
| first1 = Zhipeng
| last2 = Moroishi
| first2 = Toshiro
| last3 = Guan
| first3 = Kun-Liang
| date = 2016-01-01
| title = Mechanisms of Hippo pathway regulation
| journal = Genes & Development
| language = en
| volume = 30
| issue = 1
| pages = 1–17
| doi = 10.1101/gad.274027.115
| issn = 0890-9369
| pmc = 4701972
| pmid = 26728553
}}</ref><ref>{{Cite journal
| last1 = Meng
| first1 = Zhipeng
| last2 = Moroishi
| first2 = Toshiro
| last3 = Mottier-Pavie
| first3 = Violaine
| last4 = Plouffe
| first4 = Steven W.
| last5 = Hansen
| first5 = Carsten G.
| last6 = Hong
| first6 = Audrey W.
| last7 = Park
| first7 = Hyun Woo
| last8 = Mo
| first8 = Jung-Soon
| last9 = Lu
| first9 = Wenqi
| date = 2015-10-05
| title = MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway
| journal = Nature Communications
| language = en
| volume = 6
| pages = 8357
| doi = 10.1038/ncomms9357
| pmc = 4600732
| pmid = 26437443
| bibcode = 2015NatCo...6.8357M
}}</ref>
== Interactions ==
MAP4K2 has been shown to [[Protein-protein interaction|interact]] with [[RAB8A]]<ref name=pmid8643544>{{cite journal | vauthors = Ren M, Zeng J, De Lemos-Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD | title = In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 10 | pages = 5151–5 | date = May 1996 | pmid = 8643544 | pmc = 39423 | doi = 10.1073/pnas.93.10.5151 | bibcode = 1996PNAS...93.5151R | doi-access = free }}</ref> and [[TRAF2]].<ref name=pmid9712898>{{cite journal | vauthors = Yuasa T, Ohno S, Kehrl JH, Kyriakis JM | title = Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 35 | pages = 22681–92 | date = Aug 1998 | pmid = 9712898 | doi = 10.1074/jbc.273.35.22681 | doi-access = free }}</ref>
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Vionnet N, Stoffel M, Takeda J, Yasuda K, Bell GI, Zouali H, Lesage S, Velho G, Iris F, Passa P | title = Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus | journal = Nature | volume = 356 | issue = 6371 | pages = 721–2 | date = Apr 1992 | pmid = 1570017 | doi = 10.1038/356721a0 | bibcode = 1992Natur.356..721V | s2cid = 4310834 }}
* {{cite journal | vauthors = Matsutani A, Janssen R, Donis-Keller H, Permutt MA | title = A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p | journal = Genomics | volume = 12 | issue = 2 | pages = 319–25 | date = Feb 1992 | pmid = 1740341 | doi = 10.1016/0888-7543(92)90380-B }}
* {{cite journal | vauthors = Pombo CM, Kehrl JH, Sánchez I, Katz P, Avruch J, Zon LI, Woodgett JR, Force T, Kyriakis JM | title = Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase | journal = Nature | volume = 377 | issue = 6551 | pages = 750–4 | date = Oct 1995 | pmid = 7477268 | doi = 10.1038/377750a0 | bibcode = 1995Natur.377..750P | s2cid = 4328522 }}
* {{cite journal | vauthors = Ren M, Zeng J, De Lemos-Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD | title = In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 10 | pages = 5151–5 | date = May 1996 | pmid = 8643544 | pmc = 39423 | doi = 10.1073/pnas.93.10.5151 | bibcode = 1996PNAS...93.5151R | doi-access = free }}
* {{cite journal | vauthors = Guru SC, Agarwal SK, Manickam P, Olufemi SE, Crabtree JS, Weisemann JM, Kester MB, Kim YS, Wang Y, Emmert-Buck MR, Liotta LA, Spiegel AM, Boguski MS, Roe BA, Collins FS, Marx SJ, Burns L, Chandrasekharappa SC | title = A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus | journal = Genome Research | volume = 7 | issue = 7 | pages = 725–35 | date = Jul 1997 | pmid = 9253601 | pmc = 310681 | doi = 10.1101/gr.7.7.725 }}
* {{cite journal | vauthors = Yuasa T, Ohno S, Kehrl JH, Kyriakis JM | title = Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 35 | pages = 22681–92 | date = Aug 1998 | pmid = 9712898 | doi = 10.1074/jbc.273.35.22681 | doi-access = free }}
* {{cite journal | vauthors = Chadee DN, Yuasa T, Kyriakis JM | title = Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2 | journal = Molecular and Cellular Biology | volume = 22 | issue = 3 | pages = 737–49 | date = Feb 2002 | pmid = 11784851 | pmc = 133545 | doi = 10.1128/MCB.22.3.737-749.2002 }}
* {{cite journal | vauthors = Wissing J, Jänsch L, Nimtz M, Dieterich G, Hornberger R, Kéri G, Wehland J, Daub H | title = Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry | journal = Molecular & Cellular Proteomics | volume = 6 | issue = 3 | pages = 537–47 | date = Mar 2007 | pmid = 17192257 | doi = 10.1074/mcp.T600062-MCP200 | doi-access = free | hdl = 10033/19756 | hdl-access = free }}
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