Dynamic positive feedback phosphorylation of mixed lineage kinase 3 by JNK reversibly regulates its distribution to triton-soluble domains

被引:28
作者
Schachter, Karen A.
Du, Yan
Lin, Anning
Gallo, Kathleen A.
机构
[1] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA
[2] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA
[3] Michigan State Univ, Cell & Mol Biol Program, E Lansing, MI 48824 USA
[4] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA
关键词
D O I
10.1074/jbc.M603324200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MLK3 (mixed lineage kinase 3) is a widely expressed, mammalian serine/threonine protein kinase that activates multiple MAPK pathways. Previously our laboratory used in vivo labeling/mass spectrometry to identify phosphorylation sites of activated MLK3. Seven of 11 identified sites correspond to the consensus motif for phosphorylation by proline-directed kinases. Based on these results, we hypothesized that JNK, or another proline-directed kinase, phosphorylates MLK3 as part of a feedback loop. Herein we provide evidence that MLK3 can be phosphorylated by JNK in vitro and in vivo. Blockade of JNK results in dephosphorylation of MLK3. The hypophosphorylated form of MLK3 is inactive and redistributes to a Triton-insoluble fraction. Recovery from JNK inhibition restores MLK3 solubility and activity, indicating that the redistribution process is reversible. This work describes a novel mode of regulation of MLK3, by which JNK-mediated feedback phosphorylation of MLK3 regulates its activation and deactivation states by cycling between Triton-soluble and Triton-insoluble forms.
引用
收藏
页码:19134 / 19144
页数:11
相关论文
共 67 条
[31]   Positive feedback between MAP kinase and Mos during Xenopus oocyte maturation [J].
Matten, WT ;
Copeland, TD ;
Ahn, NG ;
VandeWoude, GF .
DEVELOPMENTAL BIOLOGY, 1996, 179 (02) :485-492
[32]   Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5 [J].
Meijer, L ;
Borgne, A ;
Mulner, O ;
Chong, JPJ ;
Blow, JJ ;
Inagaki, N ;
Inagaki, M ;
Delcros, JG ;
Moulinoux, JP .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 243 (1-2) :527-536
[33]   Regulation of protein kinase cascades by protein phosphatase 2A [J].
Millward, TA ;
Zolnierowicz, S ;
Hemmings, BA .
TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (05) :186-191
[34]   Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress [J].
Morita, K ;
Saitoh, M ;
Tobiume, K ;
Matsuura, H ;
Enomoto, S ;
Nishitoh, H ;
Ichijo, H .
EMBO JOURNAL, 2001, 20 (21) :6028-6036
[35]   Evidence for a role of mixed lineage kinases in neuronal apoptosis [J].
Mota, M ;
Reeder, M ;
Chernoff, J ;
Bazenet, CE .
JOURNAL OF NEUROSCIENCE, 2001, 21 (14) :4949-4957
[36]   Mixed lineage kinase-dependent JNK activation is governed by interactions of scaffold protein JIP with MAPK module components [J].
Nihalani, D ;
Meyer, D ;
Pajni, S ;
Holzman, LB .
EMBO JOURNAL, 2001, 20 (13) :3447-3458
[37]   Caveolin interaction with protein kinase C - Isoenzyme-dependent regulation of kinase activity by the caveolin scaffolding domain peptide [J].
Oka, N ;
Yamamoto, M ;
Schwencke, C ;
Kawabe, J ;
Ebina, T ;
Ohno, S ;
Couet, J ;
Lisanti, MP ;
Ishikawa, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (52) :33416-33421
[38]   Activated JNK phosphorylates the C-terminal domain of MLK2 that is required for MLK2-induced apoptosis [J].
Phelan, DR ;
Price, G ;
Liu, YF ;
Dorow, DS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (14) :10801-10810
[39]   Stress-induced inhibition of the NF-κB signaling pathway results from the insolubilization of the IκB kinase complex following its dissociation from heat shock protein 90 [J].
Pittet, JF ;
Lee, H ;
Pespeni, M ;
O'Mahony, A ;
Roux, J ;
Welch, WJ .
JOURNAL OF IMMUNOLOGY, 2005, 174 (01) :384-394
[40]   The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1 [J].
Rana, A ;
Gallo, K ;
Godowski, P ;
Hirai, S ;
Ohno, S ;
Zon, L ;
Kyriakis, JM ;
Avruch, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (32) :19025-19028