scholarly journals Synergistic Interaction of MEK Kinase 2, c-Jun N-Terminal Kinase (JNK) Kinase 2, and JNK1 Results in Efficient and Specific JNK1 Activation

2000 ◽  
Vol 20 (7) ◽  
pp. 2334-2342 ◽  
Author(s):  
Jinke Cheng ◽  
Jianhua Yang ◽  
Ying Xia ◽  
Michael Karin ◽  
Bing Su
Keyword(s):  
Complex Formation ◽  
Molecular Basis ◽  
Synergistic Interaction ◽  
Specific Flow ◽  
Mitogen Activated Protein Kinases ◽  
Mapk Kinase ◽  
Signaling Complex ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Flow Of Information

ABSTRACT Mitogen-activated protein kinases (MAPKs) are activated through cascades or modules consisting of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK). Investigating the molecular basis of activation of the c-Jun N-terminal kinase (JNK) subgroup of MAPK by the MAPKKK MEKK2, we found that strong and specific JNK1 activation by MEKK2 was mediated by the MAPKK JNK kinase 2 (JNKK2) rather than by JNKK1 through formation of a tripartite complex consisting of MEKK2, JNKK2, and JNK1. No scaffold protein was required for the MEKK2-JNKK2-JNK1 tripartite-complex formation. Expression of JNK1, JNKK2, and MEKK2 significantly augmented the coprecipitation of, respectively, MEKK2-JNKK2, MEKK2-JNK1, and JNKK2-JNK1, indicating that the interaction of MEKK2, JNKK2, and JNK1 is synergistic. Finally, the JNK1 was activated more efficiently in the MEKK2-JNKK2-JNK1 complex than was the JNK1 excluded from the complex. Thus, formation of a signaling complex through synergistic interaction of a MAPKKK, a MAPKK, and a MAPK molecule like MEKK2-JNKK2-JNK1 is likely to be responsible for the efficient, specific flow of information via MAPK cascades.

scholarly journals Mip1, an MEKK2-Interacting Protein, Controls MEKK2 Dimerization and Activation

2005 ◽  
Vol 25 (14) ◽  
pp. 5955-5964 ◽  
Author(s):  
Jinke Cheng ◽  
Dongyu Zhang ◽  
Kihwan Kim ◽  
Yingxin Zhao ◽  
Yingming Zhao ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Wide Spectrum ◽  
Gene Activation ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Mapk Kinase ◽  
Mapk Cascades ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Molecular Aspects

ABSTRACT Mitogen-activated protein kinase (MAPK) cascades are central components of the intracellular signaling networks used by eukaryotic cells to respond to a wide spectrum of extracellular stimuli. An MAPK is activated by an MAPK kinase, which in turn is activated by an MAPK kinase kinase (MAP3K). However, little is known about the molecular aspects of the regulation and activation of large numbers of MAP3Ks that are crucial in relaying upstream receptor-mediated signals through the MAPK cascades to induce various physiological responses. In this study, we identified a novel MEKK2-interacting protein, Mip1, that regulates MEKK2 dimerization and activation by forming a complex with inactive and nonphosphorylated MEKK2. In particular, Mip1 prevented MEKK2 activation by blocking MEKK2 dimer formation, which in turn blocked JNKK2, c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 5, and AP-1 reporter gene activation by MEKK2. Furthermore, we found that the endogenous Mip1-MEKK2 complex was dissociated transiently following epidermal growth factor stimulation. In contrast, the knockdown of Mip1 expression by siRNA augmented the MEKK2-mediated JNK and AP-1 reporter activation. Together, our data suggest a novel model for MEKK2 regulation and activation.

Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human

1999 ◽  
Vol 79 (1) ◽  
pp. 143-180 ◽  
Author(s):  
CHRISTIAN WIDMANN ◽  
SPENCER GIBSON ◽  
MATTHEW B. JARPE ◽  
GARY L. JOHNSON
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Mammalian Cells ◽  
Mitogen Activated Protein Kinase ◽  
Cell Physiology ◽  
Mitogen Activated Protein Kinases ◽  
Mapk Kinase ◽  
Mapk Pathways ◽  
Mitogen Activated Protein ◽  
Sequential Activation

Widmann, Christian, Spencer Gibson, Matthew B. Jarpe, and Gary L. Johnson. Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human. Physiol. Rev. 79: 143–180, 1999. — Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MAPK pathways is a three-component module conserved from yeast to humans. The MAPK module includes three kinases that establish a sequential activation pathway comprising a MAPK kinase kinase (MKKK), MAPK kinase (MKK), and MAPK. Currently, there have been 14 MKKK, 7 MKK, and 12 MAPK identified in mammalian cells. The mammalian MAPK can be subdivided into five families: MAPKerk1/2, MAPKp38, MAPKjnk, MAPKerk3/4, and MAPKerk5. Each MAPK family has distinct biological functions. In Saccharomyces cerevisiae, there are five MAPK pathways involved in mating, cell wall remodelling, nutrient deprivation, and responses to stress stimuli such as osmolarity changes. Component members of the yeast pathways have conserved counterparts in mammalian cells. The number of different MKKK in MAPK modules allows for the diversity of inputs capable of activating MAPK pathways. In this review, we define all known MAPK module kinases from yeast to humans, what is known about their regulation, defined MAPK substrates, and the function of MAPK in cell physiology.

scholarly journals A phylogenetic study of the members of the MAPK and MEK families across Viridiplantae

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250584
Author(s):  
José Manuel González-Coronel ◽  
Gustavo Rodríguez-Alonso ◽  
Ángel Arturo Guevara-García
Keyword(s):  
Early Stage ◽  
Genomic Analysis ◽  
Phylogenetic Study ◽  
Related Protein ◽  
Mitogen Activated Protein Kinases ◽  
Mapk Kinase ◽  
Mitogen Activated Protein ◽  
Phosphorylation Cascade ◽  
Activity Of Enzymes ◽  
Complicated Task

Protein phosphorylation is regulated by the activity of enzymes generically known as kinases. One of those kinases is Mitogen-Activated Protein Kinases (MAPK), which operate through a phosphorylation cascade conformed by members from three related protein kinase families namely MAPK kinase kinase (MEKK), MAPK kinase (MEK), and MAPK; these three acts hierarchically. Establishing the evolution of these proteins in the plant kingdom is an interesting but complicated task because the current MAPK, MAPKK, and MAPKKK subfamilies arose from duplications and subsequent sub-functionalization during the early stage of the emergence of Viridiplantae. Here, anin silicogenomic analysis was performed on 18 different plant species, which resulted in the identification of 96 genes not previously annotated as components of the MAPK (70) and MEK (26) families. Interestingly, a deeper analysis of the sequences encoded by such genes revealed the existence of putative domains not previously described as signatures of MAPK and MEK kinases. Additionally, our analysis also suggests the presence of conserved activation motifs besides the canonical TEY and TDY domains, which characterize the MAPK family.

MEKK3-mediated signaling to p38 kinase and TonE in hypertonically stressed kidney cells

2006 ◽  
Vol 291 (4) ◽  
pp. F874-F881 ◽  
Author(s):  
Ranjit Padda ◽  
Ann Wamsley-Davis ◽  
Michael C. Gustin ◽  
Rebekah Ross ◽  
Christina Yu ◽  
...  
Keyword(s):  
Mdck Cells ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
P38 Kinase ◽  
Small Interference Rna ◽  
Transfected Cells ◽  
Mapk Kinase ◽  
Empty Vector ◽  
Mapk Cascades ◽  
Mitogen Activated Protein

Mitogen-activated protein kinase (MAPK) cascades contain a trio of kinases, MAPK kinase kinase (MKKK) → MAPK kinase (MKK) → MAPK, that mediate a variety of cellular responses to different signals including hypertonicity. The signaling response to hypertonicity is conserved across evolution from yeast to mammals in that it involves activation of p38/SAPK. However, very little is known about which upstream protein kinases mediate activation of p38 by hypertonicity in mammals. The MKKKs, MEKK3 and MEKK4, are upstream regulators of p38 in many cells. To investigate these signaling proteins as potential activators of p38 in the hypertonicity response, we generated stably transfected MDCK cells that express activated versions of MEKK3 or MEKK4, utilized RNA interference to deplete MEKK3, and employed pharmacological inhibition of p38 kinase. MEKK3-transfected cells demonstrated increased betaine transporter (BGT1) mRNA levels and upregulated tonicity enhancer (TonE)-driven luciferase activity under isotonic (basal) and hypertonic conditions compared with empty vector-transfected controls; small-interference RNA-mediated depletion of MEKK3 downregulated the activity of p38 kinase and decreased the expression of BGT1 mRNA. p38 Kinase inhibition abolished the effects of MEKK3 activation on BGT1 induction. In contrast, the response to hypertonicity in MEKK4-kA-transfected cells was similar to that observed in empty vector-transfected controls. Our data are consistent with the existence of an input from MEKK3 →→ p38 kinase →→ TonE.

scholarly journals Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Yong Son ◽  
Yong-Kwan Cheong ◽  
Nam-Ho Kim ◽  
Hun-Taeg Chung ◽  
Dae Gill Kang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinases ◽  
Reactive Oxygen ◽  
Mapk Signaling ◽  
Oxygen Species ◽  
Mitogen Activated Protein Kinases ◽  
Mapk Kinase ◽  
Mapk Pathways ◽  
Mitogen Activated Protein ◽  
P38 Mapks

Mitogen-activated protein kinases (MAPKs) are serine-threonine protein kinases that play the major role in signal transduction from the cell surface to the nucleus. MAPKs, which consist of growth factor-regulated extracellular signal-related kinases (ERKs), and the stress-activated MAPKs, c-jun NH2-terminal kinases (JNKs) and p38 MAPKs, are part of a three-kinase signaling module composed of the MAPK, an MAPK kinase (MAP2K) and an MAPK kinase (MAP3K). MAP3Ks phosphorylate MAP2Ks, which in turn activate MAPKs. MAPK phosphatases (MKPs), which recognize the TXY amino acid motif present in MAPKs, dephosphorylate and deactivate MAPKs. MAPK pathways are known to be influenced not only by receptor ligand interactions, but also by different stressors placed on the cell. One type of stress that induces potential activation of MAPK pathways is the oxidative stress caused by reactive oxygen species (ROS). Generally, increased ROS production in a cell leads to the activation of ERKs, JNKs, or p38 MAPKs, but the mechanisms by which ROS can activate these kinases are unclear. Oxidative modifications of MAPK signaling proteins and inactivation and/or degradation of MKPs may provide the plausible mechanisms for activation of MAPK pathways by ROS, which will be reviewed in this paper.

scholarly journals Update on the Roles of Rice MAPK Cascades

2021 ◽  
Vol 22 (4) ◽  
pp. 1679
Author(s):  
Jie Chen ◽  
Lihan Wang ◽  
Meng Yuan
Keyword(s):  
Signal Transduction ◽  
Abiotic Stress ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Developmental Regulation ◽  
Mitogen Activated Protein Kinase ◽  
Biotic And Abiotic Stress ◽  
Mapk Kinase ◽  
Mapk Cascades ◽  
Mitogen Activated Protein

The mitogen-activated protein kinase (MAPK) cascades have been validated playing critical roles in diverse aspects of plant biology, from growth and developmental regulation, biotic and abiotic stress responses, to phytohormone signal transduction or responses. A classical MAPK cascade consists of a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK), and a MAPK. From the 75 MAPKKKs, eight MAPKKs, and 15 MAPKs of rice, a number of them have been functionally deciphered. Here, we update recent advances in knowledge of the roles of rice MAPK cascades, including their components and complicated action modes, their diversified functions controlling rice growth and developmental responses, coordinating resistance to biotic and abiotic stress, and conducting phytohormone signal transduction. Moreover, we summarize several complete MAPK cascades that harbor OsMAPKKK-OsMAPKK-OsMAPK, their interaction with different upstream components and their phosphorylation of diverse downstream substrates to fulfill their multiple roles. Furthermore, we state a comparison of networks of rice MAPK cascades from signal transduction crosstalk to the precise selection of downstream substrates. Additionally, we discuss putative concerns for elucidating the underlying molecular mechanisms and molecular functions of rice MAPK cascades in the future.

scholarly journals The Role of Specific Mitogen-Activated Protein Kinase Signaling Cascades in the Regulation of Steroidogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Pulak R. Manna ◽  
Douglas M. Stocco
Keyword(s):  
Protein Kinase ◽  
Regulatory Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Steroid Synthesis ◽  
Mapk Kinase ◽  
Mapk Cascades ◽  
Steroidogenic Cell ◽  
Mitogen Activated Protein

Mitogen-activated protein kinases (MAPKs) comprise a family of serine/threonine kinases that are activated by a large variety of extracellular stimuli and play integral roles in controlling many cellular processes, from the cell surface to the nucleus. The MAPK family includes four distinct MAPK cascades, that is, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, c-Jun N-terminal kinase or stress-activated protein kinase, and ERK5. These MAPKs are essentially operated through three-tiered consecutive phosphorylation events catalyzed by a MAPK kinase kinase, a MAPK kinase, and a MAPK. MAPKs lie in protein kinase cascades. The MAPK signaling pathways have been demonstrated to be associated with events regulating the expression of the steroidogenic acute regulatory protein (StAR) and steroidogenesis in steroidogenic tissues. However, it has become clear that the regulation of MAPK-dependent StAR expression and steroid synthesis is a complex process and is context dependent. This paper summarizes the current level of understanding concerning the roles of the MAPK signaling cascades in the regulation of StAR expression and steroidogenesis in different steroidogenic cell models.

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