MAP4K2

Mitogen-activated protein kinase kinase kinase kinase 2
Identifiers
Symbols	MAP4K2 ; BL44; GCK; RAB8IP
External IDs	OMIM: 603166 MGI: 1346883 HomoloGene: 3370 ChEMBL: 5330 GeneCards: MAP4K2 Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein serine/threonine kinase activity • protein binding • ATP binding • MAP kinase kinase kinase kinase activity • mitogen-activated protein kinase kinase kinase binding Cellular component • Golgi membrane • cytoplasm • basolateral plasma membrane Biological process • activation of MAPKKK activity • protein phosphorylation • vesicle targeting • immune response • JNK cascade • activation of JUN kinase activity • regulation of mitotic cell cycle • intracellular signal transduction • regulation of apoptotic process • innate immune response • positive regulation of JNK cascade Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5871	26412
Ensembl	ENSG00000168067	ENSMUSG00000024948
UniProt	Q12851	Q61161
RefSeq (mRNA)	NM_001307990	NM_001291787
RefSeq (protein)	NP_001294919	NP_001278716
Location (UCSC)	Chr 11: 64.78 – 64.8 Mb	Chr 19: 6.34 – 6.36 Mb
PubMed search

Mitogen-activated protein kinase kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP4K2 gene.^[1][2]

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.^[2] A recent study showed that MAP4K2 is a direct kinase of LATS1/2 and thus regulates the Hippo pathway effectors YAP and TAZ.^[3][4]

Interactions

MAP4K2 has been shown to interact with RAB8A^[5] and TRAF2.^[6]

References

1. Katz P, Whalen G, Kehrl JH (Jun 1994). "Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center". The Journal of Biological Chemistry 269 (24): 16802–9. PMID 7515885.
2. "Entrez Gene: MAP4K2 mitogen-activated protein kinase kinase kinase kinase 2".
3. Meng, Zhipeng; Moroishi, Toshiro; Guan, Kun-Liang (2016-01-01). "Mechanisms of Hippo pathway regulation". Genes & Development 30 (1): 1–17. doi:10.1101/gad.274027.115. ISSN 0890-9369. PMC 4701972. PMID 26728553.
4. Meng, Zhipeng; Moroishi, Toshiro; Mottier-Pavie, Violaine; Plouffe, Steven W.; Hansen, Carsten G.; Hong, Audrey W.; Park, Hyun Woo; Mo, Jung-Soon; Lu, Wenqi (2015-10-05). "MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway". Nature Communications 6: 8357. doi:10.1038/ncomms9357. PMC 4600732. PMID 26437443.
5. Ren M, Zeng J, De Lemos-Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD (May 1996). "In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase". Proceedings of the National Academy of Sciences of the United States of America 93 (10): 5151–5. doi:10.1073/pnas.93.10.5151. PMC 39423. PMID 8643544.
6. Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (Aug 1998). "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". The Journal of Biological Chemistry 273 (35): 22681–92. doi:10.1074/jbc.273.35.22681. PMID 9712898.

Further reading

• Vionnet N, Stoffel M, Takeda J, Yasuda K, Bell GI, Zouali H, Lesage S, Velho G, Iris F, Passa P (Apr 1992). "Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus". Nature 356 (6371): 721–2. doi:10.1038/356721a0. PMID 1570017.
• Matsutani A, Janssen R, Donis-Keller H, Permutt MA (Feb 1992). "A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p". Genomics 12 (2): 319–25. doi:10.1016/0888-7543(92)90380-B. PMID 1740341.
• Pombo CM, Kehrl JH, Sánchez I, Katz P, Avruch J, Zon LI, Woodgett JR, Force T, Kyriakis JM (Oct 1995). "Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase". Nature 377 (6551): 750–4. doi:10.1038/377750a0. PMID 7477268.
• Ren M, Zeng J, De Lemos-Chiarandini C, Rosenfeld M, Adesnik M, Sabatini DD (May 1996). "In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase". Proceedings of the National Academy of Sciences of the United States of America 93 (10): 5151–5. doi:10.1073/pnas.93.10.5151. PMC 39423. PMID 8643544.
• 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 (Jul 1997). "A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus". Genome Research 7 (7): 725–35. doi:10.1101/gr.7.7.725. PMC 310681. PMID 9253601.
• Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (Aug 1998). "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". The Journal of Biological Chemistry 273 (35): 22681–92. doi:10.1074/jbc.273.35.22681. PMID 9712898.
• Chadee DN, Yuasa T, Kyriakis JM (Feb 2002). "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2". Molecular and Cellular Biology 22 (3): 737–49. doi:10.1128/MCB.22.3.737-749.2002. PMC 133545. PMID 11784851.
• Wissing J, Jänsch L, Nimtz M, Dieterich G, Hornberger R, Kéri G, Wehland J, Daub H (Mar 2007). "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry". Molecular & Cellular Proteomics 6 (3): 537–47. doi:10.1074/mcp.T600062-MCP200. PMID 17192257.