High impact information on Map3k2

• Live cell fluorescence imaging of T cell MEKK2: redistribution and activation in response to antigen stimulation of the T cell receptor [1].
• However, the identification of MEK5alpha mutants with selective binding defect demonstrates that the MEK5/ERK5 interaction does not rely on the binding of MEK5alpha to MEKK2 via their respective PB1 domains [2].
• Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation [3].
• Furthermore, TCR-mediated c-Jun N-terminal kinase activation was not blocked but moderately enhanced in Mekk2(-/-) T cells [4].
• In conclusion, we found that MEKK2 may be required for controlling the strength of TCR/CD3 signaling [4].

Biological context of Map3k2

• Consistently, Mekk2(-/-) thymocytes were more susceptible than wild-type thymocytes to anti-CD3 MAb-induced cell death [4].
• Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction [4].
• MEKK2 also synergized with anti-CD3 antibody to activate JNK in T cells, and stimulation of T cells led to induction of MEKK2 tyrosine phosphorylation [5].

Anatomical context of Map3k2

• Major subsets of thymic and spleen T cells in Mekk2-deficient mice were indistinguishable from those in wild-type mice [4].
• B-cell development appeared to proceed similarly in the bone marrow of Mekk2-deficient and wild-type mice [4].
• Northern blot analysis showed that MEKK2 was ubiquitously expressed, with the highest level in peripheral blood leukocytes [5].
• Inhibition of ERK5, MEK5 activation or activation of MEKK2-deficient mast cells was associated with inhibition of MEF2C phosphorylation and a decrease in c-Jun expression [6].

Associations of Map3k2 with chemical compounds

• Significantly, the JNK activation induced by anti-CD3 and anti-CD28 antibodies, but not by 12-O-tetradecanoylphorbol-13-acetate and Ca(2+) ionophore A23187, was inhibited by dominant negative MEKK2 mutants [5].

Regulatory relationships of Map3k2

• Thus, MEKK2 regulates AP-1 activity at two levels, by regulating both expression of AP-1 components and c-Jun N-terminal phosphorylation [7].
• Cytokine production was stimulated by over-expression of PKC in cells from MEKK2-deficient and wild-type mice [8].

Other interactions of Map3k2

• However, Mekk2(-/-) T-cell proliferation was augmented in response to anti-CD3 monoclonal antibody (MAb) stimulation, and these T cells produced more interleukin 2 and gamma interferon than did the wild-type T cells, suggesting that MEKK2 may be involved in controlling the strength of T-cell receptor (TCR) signaling [4].
• Importantly, disrupted expression of MEKK2, a related MAPK kinase kinase, had no effect on uPA activity [9].
• The purpose of this study was to define the specific role of MEKK2, an MKKK, in MAPK regulation and cell function [7].

Analytical, diagnostic and therapeutic context of Map3k2

• Furthermore, co-immunoprecipitation of MEKK2 and MEK5 from cell lysates shows that they form a complex in vivo [10].
• In this study, immunocytochemistry and live cell fluorescence imaging demonstrate that T cell MEK kinase 2 (MEKK2) is translocated to the T cell/antigen-presenting cell interface in response to antigen activation [1].

References