Alternative titles; symbols
HGNC Approved Gene Symbol: MAP4K2
Cytogenetic location: 11q13.1 Genomic coordinates (GRCh38): 11:64,784,918-64,803,214 (from NCBI)
B lymphocytes that reside in the germinal center of lymphoid follicles are functionally and phenotypically distinct from those residing in the surrounding mantle zone. Various regulatory and structural genes control a complex series of differentiation and selection steps through which B cells that exit the germinal center of lymphoid follicles must pass. In differential hybridization studies to identify some of these genes, Katz et al. (1994) isolated a novel gene based on its preferential expression in tonsillar germinal center B lymphocytes. The complete nucleotide sequence predicted an 819-amino acid protein, named GC (for 'germinal center') kinase, with homology to serine-threonine protein kinases. Its catalytic domain was 39% and 37% identical to those of S. cerevisiae STE20 and Drosophila ninaC proteins, respectively. Northern blot analysis revealed expression of a 2.9-kb mRNA in several human tissues, including brain, lung, and placenta. In situ hybridization of tonsil tissue demonstrated preferential hybridization to the germinal center region. The expressed protein phosphorylated casein and myelin basic protein in in vitro kinase assays.
Pombo et al. (1995) showed that GC kinase specifically activates the SAPK (601335) pathway. They also showed that GCK is activated in situ by TNF-alpha (191160), a potent SAPK agonist. The authors suggested that the SAPK pathway may be active in the differentiation and selection of B cells in the germinal center.
Ren et al. (1996) identified a mouse protein based on its interaction with the vesicular transport protein Rab8 (165040). This mouse protein, termed Rab8ip, and GC kinase shared 93% amino acid sequence identity. Rab8ip/GC kinase had serine/threonine protein kinase activity manifested both as autophosphorylation and phosphorylation of casein and myelin basic protein. Based on its interaction with Rab8, the authors suggested that Rab8ip/GC kinase may modulate secretion in response to stress stimuli.
Guru et al. (1997) mapped and sequenced the MEN I (MEN1; 131100) genomic region at 11q13. They identified MAP4K2 in this region between PYGM (608455) and marker D11S4936.
Guru, S. C., Agarwal, S. K., Manickam, P., Olufemi, S.-E., Crabtree, J. S., Weisemann, J. M., Kester, M. B., Kim, Y. S., Wang, Y., Emmert-Buck, M. R., Liotta, L. A., Spiegel, A. M., Boguski, M. S., Roe, B. A., Collins, F. S., Marx, S. J., Burns, L., Chandrasekharappa, S. C. A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus. Genome Res. 7: 725-735, 1997. [PubMed: 9253601] [Full Text: https://doi.org/10.1101/gr.7.7.725]
Katz, P., Whalen, G., Kehrl, J. H. Differential expression of a novel protein kinase in human B lymphocytes: preferential localization in the germinal center. J. Biol. Chem. 269: 16802-16809, 1994. [PubMed: 7515885]
Pombo, C. M., Kehrl, J. H., Sanchez, I., Katz, P., Avruch, J., Zon, L. I., Woodgett, J. R., Force, T., Kyriakis, J. M. Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature 377: 750-754, 1995. [PubMed: 7477268] [Full Text: https://doi.org/10.1038/377750a0]
Ren, M., Zeng, J., De Lemos-Chiarandini, C., Rosenfeld, M., Adesnik, M., Sabatini, D. D. In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase. Proc. Nat. Acad. Sci. 93: 5151-5155, 1996. [PubMed: 8643544] [Full Text: https://doi.org/10.1073/pnas.93.10.5151]