Alternative titles; symbols
HGNC Approved Gene Symbol: MAPK8IP2
Cytogenetic location: 22q13.33 Genomic coordinates (GRCh38): 22:50,600,793-50,613,978 (from NCBI)
Using a cDNA fragment of JIP1 (MAPK8IP1; 604641) as probe, Yasuda et al. (1999) cloned MAPK8IP2, which they designated JIP2, from a brain cDNA library. The deduced 824-amino acid protein contains 2 N-terminal acidic regions, a JNK (601158)-binding domain, 2 central proline-rich regions, a third acidic region, an SRC homology-3 domain, and a phosphotyrosine-binding domain. Northern blot analysis revealed expression of JIP2 in adult and fetal brain, and mRNA dot blot analysis detected low expression in uterus, prostate, colon, testis, ovary, pancreas, adrenal gland, thyroid gland, and salivary gland.
By RT-PCR and RACE of insulinoma, glucagonoma, and brain RNA, Negri et al. (2000) cloned MAPK8IP2, which they designated IB2. The deduced 797-amino acid protein has a calculated molecular mass of about 84 kD. Northern blot analysis revealed transcripts of about 4.0 and 2.8 kb expressed exclusively in brain and pancreas, respectively. Expression was ubiquitous within specific brain regions, but was more abundant in cerebellum, pituitary gland, occipital lobe, and amygdala. RT-PCR detected expression in glucagonoma and insulinoma cells and in mouse pancreatic beta cells, but not in other tissues or cell types tested, including liver, kidney, pheochromocytoma, and HeLa cells.
By coimmunoprecipitation assays, Yasuda et al. (1999) determined that the mammalian scaffold proteins JIP1 and JIP2 interact to form oligomeric complexes, and they both coimmunoprecipitated with DLK (600447), MLK2 (600137), MLK3 (600050), MKK7 (603014), and JNK. The C-terminal portions of JIP1 and JIP2 were sufficient for interaction with MLK3 and MKK7, and the N-terminal portions interacted with JNK. Ten different JNK isoforms bound both JIP proteins, although binding affinities differed between them. Double-label immunofluorescence analysis indicated that endogenous rat Jip1 and Jip2 colocalized in peripheral cytoplasmic projections extended at the cell surface of rat insulinoma cells. Yasuda et al. (1999) concluded that the JIP proteins function by aggregating components of a MAP kinase module, including MLK, MKK7, and JNK, and facilitate signal transmission by the protein kinase cascade.
Negri et al. (2000) confirmed interaction between IB2 and JNK and between IB2 and the JNK kinase, MKK7. Ectopic expression of the JNK-binding domain of IB2 in a mouse pancreatic beta-cell line decreased interleukin-1-beta (IL1B; 147720)-induced cell death. Negri et al. (2000) hypothesized that IB2 may represent a candidate gene for diabetes.
Yasuda et al. (1999) determined that the MAPK8IP2 gene contains 12 exons.
By genomic sequence analysis, Negri et al. (2000) mapped the MAPK8IP2 gene to the telomeric end of chromosome 22q13.
Negri, S., Oberson, A., Steinmann, M., Sauser, C., Nicod, P., Waeber, G., Schorderet, D. F., Bonny, C. cDNA cloning and mapping of a novel islet-brain/JNK-interacting protein. Genomics 64: 324-330, 2000. [PubMed: 10756100] [Full Text: https://doi.org/10.1006/geno.2000.6129]
Yasuda, J., Whitmarsh, A. J., Cavanagh, J., Sharma, M., Davis, R. J. The JIP group of mitogen-activated protein kinase scaffold proteins. Molec. Cell. Biol. 19: 7245-7254, 1999. [PubMed: 10490659] [Full Text: https://doi.org/10.1128/MCB.19.10.7245]