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K Deacon

Publications and source records attributed to K Deacon.

5 recordsLinked to original sources
PubMed1999

MEK kinase 3 directly activates MKK6 and MKK7, specific activators of the p38 and c-Jun NH2-terminal kinases.

Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) activates the c-Jun NH2-terminal kinase (JNK) pathway, although no substrates for MEKK3 have been identified. We have examined the regulation by MEKK3 of MAPK kinase 7 (MKK7) and MKK6, two novel MAPK kinases specific for JNK and p38, respectively. Coexpression of MKK7 with MEKK3 in COS-7 cells enhanced MKK7 autophosphorylation and its ability to activate recombinant JNK1 in vitro. MKK6 autophosphorylation and in vitro activation of p38alpha were also observed following coexpression of MKK6 with MEKK3. MEKK2, a closely related homologue of MEKK3, also activated MKK7 and MKK6 in COS-7 cells. Importantly, immunoprecipitates of either MEKK3 or MEKK2 directly activated recombinant MKK7 and MKK6 in vitro. These data identify MEKK3 as a MAPK kinase kinase specific for MKK7 and MKK6 in the JNK and p38 pathways. We have also examined whether MEKK3 or MEKK2 activates p38 in intact cells using MAPK-activated protein kinase-2 (MAPKAPK2) as an affinity ligand and substrate. Anisomycin, sorbitol, or the expression of MEKK3 in HEK293 cells enhanced MAPKAPK2 phosphorylation, whereas MEKK2 was less effective. Furthermore, MAPKAPK2 phosphorylation induced by MEKK3 or cellular stress was abolished by the p38 inhibitor SB-203580, suggesting that MEKK3 is coupled to p38 activation in intact cells.

Animals↗
PubMed1997

Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.

We previously reported the isolation of cDNAs encoding two mammalian mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) kinase kinases, designated MEKK2 and MEKK3 (Blank, J.L., Gerwins, P., Elliott, E.M., Sather, S. and Johnson, G.L. (1996) J. Biol. Chem. 271, 5361-5368). In the present study, cotransfection experiments were used to examine the regulation by MEKK2 and MEKK3 of the dual specificity MAP kinase kinases, MKK3 and MKK4. MKK3 specifically phosphorylates and activates p38, whereas MKK4 phosphorylates and activates both p38 and JNK. Coexpression of MEKK2 or MEKK3 with MKK4 in COS-7 cells resulted in activation of MKK4, as assessed by enhanced autophosphorylation and by its ability to phosphorylate and activate recombinant JNK1 or p38 in vitro. MKK3 autophosphorylation and activation of p38 was also observed following coexpression of MKK3 with MEKK3, but not with MEKK2. Consistent with these observations, immunoprecipitated MEKK2 directly activated recombinant MKK4 in vitro but failed to activate MKK3. The sites of activating phosphorylation in MKK3 and MKK4 were identified within kinase subdomains VII and VIII. Replacement of Ser189 or Thr193 in MKK3 with Ala abolished autophosphorylation and activation of MKK3 by MEKK3. Analogous mutations in MKK4 indicated that Ser221 and, to a lesser extent, Thr225 were necessary for MKK4 activation by MEKK2 and MEKK3. These data indicate that MKK3 is preferentially activated by MEKK3, whereas MKK4 is activated both by MEKK2 and MEKK3. Consistent with these observations, MEKK2 and MEKK3 also activated JNK1 in vivo. However, MEKK3 failed to activate p38 when coexpressed in either the absence or presence of MKK3, indicating that MEKK3 is not coupled to p38 activation in vivo. These observations suggest that regulation of p38 and JNK1 pathways by MEKK3 may involve distinct mechanisms to prevent p38 activation but to allow JNK1 activation.

Animals↗
PubMed1997

A prison-based alcohol use education program: evaluation of a pilot study.

Northern Territory prisoners were followed up after release to determine the effect of an alcohol education course on their alcohol consumption, drinking group, disruptive behavior, criminal activity, family relationships, how they use their time, general health, ability to cope and take responsibility. Measures were obtained both from prisoners and key informants, and two groups of prisoners were compared: those who completed the course and others who had not done the course. A high level of correspondence was found between measures from key informants and prisoners. The prisoners attending the course showed significant improvements on all dimensions when compared to the control subjects.

Adult↗