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CBFA2T2  -  core-binding factor, runt domain, alpha...

Homo sapiens

Synonyms: EHT, ETO homologous on chromosome 20, MTG8-like protein, MTG8-related protein 1, MTGR1, ...
 
 
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Disease relevance of CBFA2T2

 

Psychiatry related information on CBFA2T2

  • Cases were classified into predominant maltreatment types according to three different schemes: Hierarchical regression analyses examined whether the HT, SFT, and EHT type classifications contributed to prediction of child behavior problems, trauma symptoms and adaptive functioning [5].
 

High impact information on CBFA2T2

  • Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis [2].
  • Transplantation of wild-type and Mtgr1-null bone marrow into irradiated wild-type mice demonstrated that the severe DSS-induced ulceration seen in Mtgr1-null mice was due to a colonic, rather than a hematologic, defect [2].
  • Mice lacking the transcriptional corepressor myeloid translocation gene related-1 (Mtgr1) display impaired secretory cell lineage development in the small intestine and an increase in proliferation in the crypts of both the small and large intestines [2].
  • Somatostatin-mediated dissociation of this complex as well as p85 tyrosine dephosphorylation correlates with sst2 tyrosine dephosphorylation on the Y(71) residue [6].
  • Biochemical and RNA-interference studies demonstrated that HPIP influences ERalpha-dependent rapid estrogen signaling by acting as a scaffold protein and recruits Src kinase and the p85 subunit of phosphatidylinositol 3-kinase to a complex with ERalpha, which in turn stimulates AKT and MAPK [7].
 

Chemical compound and disease context of CBFA2T2

  • The acute effects of the calcium entry blocker, nifedipine, on cerebral circulation were studied in 22 patients (56 +/- 5 years) with essential hypertension (EHT, WHO I-II) and 12 age-matched normal subjects [8].
  • The validity of the captopril test for primary aldosteronism (PA) was tested in patients with surgically verified PA (n = 12) or essential hypertension (EHT, n = 20) with different levels of sodium intakes [9].
 

Biological context of CBFA2T2

  • The MTGR1 gene consists of 14 exons and spans about 68 kb [10].
  • Comparison of amino acid sequences among MTGR1, MTG8, and Nervy revealed four evolutionarily conserved regions (NHR1 to NHR4) [11].
  • Despite the increase in proliferating cells, the colons of Mtgr1-null mice have a normal cell lineage distribution and normal architecture [2].
  • METHODS: Mtgr1-null mice were given 3% DSS in their drinking water for 4 days and the colons examined at various times thereafter for ulceration and for changes in proliferation and apoptosis [2].
  • This interaction takes place via the phosphorylated YMXM motifs of IRS-1 and the Src homology region 2 (SH2) domains of p85 [12].
 

Anatomical context of CBFA2T2

  • Transcripts of the MTGR1 gene were expressed ubiquitously in the human tissues and cell lines examined [10].
  • MTGR1 transcripts were ubiquitously expressed in human bone marrow cells [13].
  • Importantly, the epithelium of DSS-treated Mtgr1-null mice failed to completely regenerate, showing changes consistent with chronic colitis, even 10 weeks after a single DSS treatment [2].
  • On identifying prominent tyrosine kinase substrates in activated platelets, we confirm that several substrates correspond to proteins associated with the cytoskeleton: the 85-kD subunit of phosphatidylinositol 3-kinase, the SH3-containing and actin-associating p85, pp60Src, and pp125FAK.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
  • Neutralizing anti-TNF-alpha antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels [15].
 

Associations of CBFA2T2 with chemical compounds

  • Since this cDNA was shorter than the main mRNA (about 7.5 kb), the 5'-end of the MTGR1 cDNA was extended using Marathon Ready cDNA [10].
  • The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1 [11].
  • The MTGR1 and MTG16 proteins decreased during all trans-retinoic acid-, but not vitamin D(3)-induced differentiation of leukemic cells [13].
  • Two related cellular proteins, p80 and p85 (cortactin), become phosphorylated on tyrosine in pp60src-transformed cells and in cells stimulated with certain growth factors [16].
  • The SH2 domains of the p85 subunit of the phosphatidylinositol 3-kinase as well as of other signaling molecules were expressed in bacteria as glutathione S-transferase fusion proteins [17].
 

Other interactions of CBFA2T2

 

Analytical, diagnostic and therapeutic context of CBFA2T2

  • Immunoprecipitation analysis indicates that this region is required for AML1-MTG8 to form a stable complex with MTGR1 [11].
  • Surface plasmon resonance and molecular modeling identified the phosphorylated-Y(71) residue of a p85-binding pYXXM motif in the first sst2 intracellular loop, and p85 COOH-terminal SH2 as direct interacting domains [6].
  • One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 +/-10.7 yr; body mass index (BMI), 28.1 +/- 4.4 kg/m2; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 +/- 9.2 yr; BMI, 28.2 +/- 3.3 kg/m2; male/female ratio, 50/29) were enrolled in the study [18].
  • Cellular microinjection of a polyclonal antibody directed against the p85 subunit of PI3-kinase as well as a purified recombinant p85-SH2 domain protein also inhibited actin reorganization [19].
  • METHODS: To elucidate the relationship between myocardial sympathetic nervous activity and LVH in patients with essential hypertension EHT), we performed 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 49 patients with EHT and 17 normotensive control subjects [20].

References

  1. EHT, a new member of the MTG8/ETO gene family, maps on 20q11 region and is deleted in acute myeloid leukemias. Fracchiolla, N.S., Colombo, G., Finelli, P., Maiolo, A.T., Neri, A. Blood (1998) [Pubmed]
  2. Deletion of Mtgr1 sensitizes the colonic epithelium to dextran sodium sulfate-induced colitis. Martinez, J.A., Williams, C.S., Amann, J.M., Ellis, T.C., Moreno-Miralles, I., Washington, M.K., Gregoli, P., Hiebert, S.W. Gastroenterology (2006) [Pubmed]
  3. Differential effects of sera from normotensive and hypertensive pregnant women on Ca(2+) metabolism in normal vasular smooth muscle cells. Green, J., Assady, S., Nakhoul, F., Bick, T., Jakobi, P., Abassi, Z. J. Am. Soc. Nephrol. (2000) [Pubmed]
  4. Activation of Epstein-Barr virus/C3d receptor (gp140, CR2, CD21) on human B lymphoma cell surface triggers Cbl tyrosine phosphorylation, its association with p85 subunit, Crk-L and Syk and its dissociation with Vav. Lottin-Divoux, S., Jean, D., Le Romancer, M., Frade, R. Cell. Signal. (2006) [Pubmed]
  5. What's in a name? A comparison of methods for classifying predominant type of maltreatment. Lau, A.S., Leeb, R.T., English, D., Graham, J.C., Briggs, E.C., Brody, K.E., Marshall, J.M. Child abuse & neglect. (2005) [Pubmed]
  6. Direct binding of p85 to sst2 somatostatin receptor reveals a novel mechanism for inhibiting PI3K pathway. Bousquet, C., Guillermet-Guibert, J., Saint-Laurent, N., Archer-Lahlou, E., Lopez, F., Fanjul, M., Ferrand, A., Fourmy, D., Pichereaux, C., Monsarrat, B., Pradayrol, L., Estève, J.P., Susini, C. EMBO J. (2006) [Pubmed]
  7. An inherent role of microtubule network in the action of nuclear receptor. Manavathi, B., Acconcia, F., Rayala, S.K., Kumar, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Effects of a calcium entry blocker on cerebral circulation in essential hypertension. Miyamori, I., Yasuhara, S., Matsubara, T., Takasaki, H., Takeda, R. Journal of clinical hypertension. (1987) [Pubmed]
  9. Effects of sodium intake on the captopril test for primary aldosteronism. Naomi, S., Umeda, T., Iwaoka, T., Sato, T. Japanese heart journal. (1987) [Pubmed]
  10. Structure and expression pattern of a human MTG8/ETO family gene, MTGR1. Morohoshi, F., Mitani, S., Mitsuhashi, N., Kitabayashi, I., Takahashi, E., Suzuki, M., Munakata, N., Ohki, M. Gene (2000) [Pubmed]
  11. The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1. Kitabayashi, I., Ida, K., Morohoshi, F., Yokoyama, A., Mitsuhashi, N., Shimizu, K., Nomura, N., Hayashi, Y., Ohki, M. Mol. Cell. Biol. (1998) [Pubmed]
  12. 1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells. Hara, K., Yonezawa, K., Sakaue, H., Ando, A., Kotani, K., Kitamura, T., Kitamura, Y., Ueda, H., Stephens, L., Jackson, T.R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  13. The Leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation. Lindberg, S.R., Olsson, A., Persson, A.M., Olsson, I. Exp. Hematol. (2005) [Pubmed]
  14. Platelet tyrosine kinases and fibrinogen receptor activation. Furman, M.I., Grigoryev, D., Bray, P.F., Dise, K.R., Goldschmidt-Clermont, P.J. Circ. Res. (1994) [Pubmed]
  15. Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akt signaling pathway. Kawanaka, H., Jones, M.K., Szabo, I.L., Baatar, D., Pai, R., Tsugawa, K., Sugimachi, K., Sarfeh, I.J., Tarnawski, A.S. Hepatology (2002) [Pubmed]
  16. Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex. Wu, H., Parsons, J.T. J. Cell Biol. (1993) [Pubmed]
  17. Interactions between SH2 domains and tyrosine-phosphorylated platelet-derived growth factor beta-receptor sequences: analysis of kinetic parameters by a novel biosensor-based approach. Panayotou, G., Gish, G., End, P., Truong, O., Gout, I., Dhand, R., Fry, M.J., Hiles, I., Pawson, T., Waterfield, M.D. Mol. Cell. Biol. (1993) [Pubmed]
  18. Is leptin associated with hypertensive retinopathy? Uckaya, G., Ozata, M., Sonmez, A., Kinalp, C., Eyileten, T., Bingol, N., Koc, B., Kocabalkan, F., Ozdemir, I.C. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  19. Phosphatidylinositol 3-kinase is necessary and sufficient for insulin-stimulated stress fiber breakdown. Martin, S.S., Rose, D.W., Saltiel, A.R., Klippel, A., Williams, L.T., Olefsky, J.M. Endocrinology (1996) [Pubmed]
  20. Direct evidence of impaired cardiac sympathetic innervation in essential hypertensive patients with left ventricular hypertrophy. Kuwahara, T., Hamada, M., Hiwada, K. J. Nucl. Med. (1998) [Pubmed]
 
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