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Aliases MAP4K2, BL44, GCK, RAB8IP, mitogen-activated protein kinase kinase kinase kinase 2
External IDs MGI: 1346883 HomoloGene: 3370 GeneCards: MAP4K2
RNA expression pattern
PBB GE MAP4K2 204936 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 11: 64.78 – 64.8 Mb Chr 19: 6.34 – 6.36 Mb
PubMed search [1] [2]
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Mitogen-activated protein kinase kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP4K2 gene.[3][4]


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.[4] A recent study showed that MAP4K2 is a direct kinase of LATS1/2 and thus regulates the Hippo pathway effectors YAP and TAZ.[5][6]


MAP4K2 has been shown to interact with RAB8A[7] and TRAF2.[8]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ a b "Entrez Gene: MAP4K2 mitogen-activated protein kinase kinase kinase kinase 2". 
  5. ^ 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 4701972Freely accessible. PMID 26728553. 
  6. ^ 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 4600732Freely accessible. PMID 26437443. 
  7. ^ 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 39423Freely accessible. PMID 8643544. 
  8. ^ 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. 

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