Disease relevance of MAP3K7IP1

• Homozygous Tab1 mutant mice died, exhibiting a bloated appearance with extensive edema and hemorrhage at the late stages of gestation [1].
• Diverse mechanisms of myocardial p38 mitogen-activated protein kinase activation: evidence for MKK-independent activation by a TAB1-associated mechanism contributing to injury during myocardial ischemia [2].
• Structural anomalies were detected on routine ultrasound of the pregnancy of a 17-year-old G3 P1 TAB1 woman with sickle cell trait [3].
• Thus, we may be able to achieve therapeutic BNCT efficacy with minimal systemic toxicity or radiation-induced damage to normal tissue by administering TABP-1 using CED [4].
• In vivo evaluation of the boronated porphyrin TABP-1 in U-87 MG intracerebral human glioblastoma xenografts [4].

High impact information on MAP3K7IP1

• Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism [5].
• Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade [6].
• Injection of XIAP mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos in a TAB1-TAK1-dependent manner [7].
• Deletion and point mutations in TAB1 reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for its interaction with p38alpha [8].
• Determinants That Control the Specific Interactions between TAB1 and p38{alpha} [8].

Biological context of MAP3K7IP1

• These results indicate critical roles of Thr-187 phosphorylation in the stress-induced rapid and transient activation of TAK1 in a signaling complex containing TAB1 and TAB2 [9].
• Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis [1].
• Recent studies have revealed that the TAB1-TAK1 interaction plays an important role in signal transduction in vitro, but little is known about the role of these molecules in vivo [1].
• The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein [7].
• TAB1 and TAB1beta share the first 10 exons [10].

Anatomical context of MAP3K7IP1

• TAB1 was not expressed in naive and activated CD4(+) T cells [11].
• We provide evidence that the cGMP target cGMP-dependent protein kinase type I (PKG I) interferes with TAB1-p38 MAPK signaling to protect cardiac myocytes from I/R injury [12].
• We report on the establishment and characterization of a new human myeloma cell line (TAB1) that can be long-term maintained in the presence of conditioned medium of bone marrow stromal cells (BMCM) and a BMCM independent variant, C2-2 [13].
• Treatment with anti-IL-6 antibody partially inhibited the proliferation of TAB1 cells cultured with BMCM [13].

Associations of MAP3K7IP1 with chemical compounds

• However, the site in TAP-1 corresponding to Phe-484 of TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates the ability of TAP-1 to interact with and activate MOM-4 [14].
• However, we were unable to detect any phosphatase activity for TAB1 using a phosphopeptide or p-nitrophenyl phosphate as substrate [15].
• Surprisingly, TAB1 possesses a fold closely related to that of the PPM (Mg(2+)- or Mn(2+)-dependent protein phosphatase) family as demonstrated by the close structural similarity with protein phosphatase 2Calpha [15].
• In addition, our data suggest interference among different pathways because TAB1 had an inhibitory effect on p38alpha phosphorylation in the peroxynitrite-induced approximately 85-kDa complex [16].
• We show that TAB1-mediated p38alpha phosphorylation in MEF cells did not need MKK3/4/6, and it accounted for a small portion of the total p38alpha phosphorylation that was induced by hyperosmolarity and anisomycin [16].

Enzymatic interactions of MAP3K7IP1

• Furthermore, TAK1 is constitutively phosphorylated when ectopically overexpressed with TAB1 [17].

Regulatory relationships of MAP3K7IP1

• In addition, overexpression of TAK1 and TAB1 induced secretion of IL-2 [18].
• Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1 [19].

Other interactions of MAP3K7IP1

• TAK1 activated IKKalpha and IKKbeta in the presence of TAB1 [20].
• Taken together, our data suggest that DDR1b-collagen interaction augments the maturation of DCs in a tissue microenvironment through a unique TRAF6/TGF-beta-activated kinase 1 binding protein 1beta/p38alpha MAPK signaling cascade and contributes to the development of adaptive immune responses [21].
• Here, we characterized the molecular mechanisms of TAK1 activation by its specific activator TAB1 [19].
• MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha [22].

Analytical, diagnostic and therapeutic context of MAP3K7IP1

• As shown by co-immunoprecipitation experiments in HEK293 cells, cGMP-activated PKG I, but not constitutively active PKG I-DeltaN1-92 or PKG I mutants carrying point mutations in the N-terminal leucine-isoleucine zipper, interacted with p38 MAPK, and prevented the binding of TAB1 to p38 MAPK [12].
• During I/R in vivo, mice with a cardiac myocyte-restricted deletion of PKG I displayed a more pronounced interaction of TAB1 with p38 MAPK and a stronger phosphorylation of p38 MAPK in the myocardial area at risk during reperfusion and more apoptotic cardiac myocytes in the infarct border zone as compared with wild-type littermates [12].
• The recombinant protein TAB1 was purified by washed pellet procedures and reversed-phase HPLC [23].

References