MAP3Ks as central regulators of cell fate during development

  title={MAP3Ks as central regulators of cell fate during development},
  author={Evisabel A. Craig and Mark V. Stevens and Richard R. Vaillancourt and Todd D Camenisch},
  journal={Developmental Dynamics},
The cytoplasmic serine/threonine kinases transduce extracellular signals into regulatory events that impact cellular responses. The induction of one kinase triggers the activation of several downstream kinases, leading to the regulation of transcription factors to affect gene function. This arrangement allows for the kinase cascade to be amplified, and integrated according to the cellular context. An upstream mitogen or growth factor signal initiates a module of three kinases: a mitogen… 

Mitogen-Activated Protein Kinases and Their Scaffolding Proteins

This chapter focuses on defining the diverse mechanisms by which different MAPKs and their scaffolding proteins interact and the significance of such interactions in the regulation of specific cellular responses.

Domain Specificity of MAP3K Family Members, MLK and Tak1, for JNK Signaling in Drosophila

It is found that overexpression of the wild-type kinases stimulated JNK signaling in alternate contexts, so cells were capable of responding to both MAP3Ks, but with distinct outcomes.

Regulation of mixed-lineage kinase activation in JNK-dependent morphogenesis

The domain requirements of Drosophila Slpr, a mixed-lineage kinase, for Jun N-terminal kinase (JNK) signaling are analyzed and expression of various Slpr constructs alone or with upstream activators reveals a wide-ranging response at the cell and tissue level.

The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions.

Four MAPK cascades have been identified in the last 20 years and those are usually named according to the MAPK components that are the central building blocks of each of the cascades, and the existence of several distinct components in each tier of the different cascades is described.

Sphingosine 1-phosphate activates the MAP3K1-JNK pathway to promote epithelial movement and morphogenesis

Results of this work establish the S1PR-MAP3K1-JNK pathway as a crucial signaling mechanism for epithelial cell movement and morphogenesis.

Differential Roles of ASK1 and TAK1 in Helicobacter pylori-Induced Cellular Responses

ROS/ASK1/JNK is identified as a new signaling pathway induced by H. pylori, which regulates apoptotic cell death and reciprocal regulation between ASK1 and TAK1 in H.pylori-related responses is found.

Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells

Novel APOBEC1 target 1 (Nat1) is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1) and ribosomal proteins, which show that Nat1 is involved in the translation of proteins that are required for cell differentiation.



MEKK1 Binds Raf-1 and the ERK2 Cascade Components*

It is demonstrated that endogenous MEKK1 binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting that it can assemble all three proteins of the ERK1/2 MAP kinase module.

Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption.

Loss of MEKK1 expression resulted in a greater apoptotic response of cells to hyperosmolarity and microtubule disruption, and activated JNK normally in response to heat shock, anisomycin, and ultraviolet irradiation.

The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems

Evidence supporting a role for MEKK4 in mediating actin recovery following osmotic shock in mammalian cells is highlighted, particularly in yeast systems adapting to specific external stimuli.

Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and p38 Signaling Pathways

Overexpression of ASK1 induced apoptotic cell death, andASK1 was activated in cells treated with tumor necrosis factor-α, and TNF-α-induced apoptosis was inhibited by a catalytically inactive form of AsK1.

MEKK2 regulates the coordinate activation of ERK5 and JNK in response to FGF‐2 in fibroblasts

The purpose of this study was to define the specific role of MEKK2, an MKKK, in MAPK regulation and cell function, and demonstrate specificity ofMEKK2 in FGF‐2 receptor signaling and control of cytokine gene expression.

Role of MLK3 in the Regulation of Mitogen-Activated Protein Kinase Signaling Cascades

It is shown that MLK3 contributes to the TNF signaling pathway that activates JNK, and targeted disruption of the murine Mlk3 gene is examined to demonstrate this.

MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration.

  • Y. XiaC. Makris M. Karin
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
Using MEKK1-deficient embryonic stem cells prepared by gene targeting, the function of the MAP3K MEK kinase 1 (MEKK1) in proinflammatory signaling is examined and it is found that it is required for JNK activation by diverse proinflammatory stimuli, including tumor necrosis factor alpha, IL-1, double-stranded RNA, and lipopolysaccharide.

Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction

Results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-β superfamily members.

Expression of mitogen‐activated protein kinase pathways during postnatal development of rat heart

Tissue distribution studies revealed that most of the protein kinases that were up‐regulated during heart development tended to be preferentially expressed in heart, whereas the downregulatedprotein kinases were generally expressed inheart at relatively lesser amounts than in most of other tissues.

Cloning of a Novel Mitogen-activated Protein Kinase Kinase Kinase, MEKK4, That Selectively Regulates the c-Jun Amino Terminal Kinase Pathway*

MEKK4 has a putative pleckstrin homology domain and a proline-rich motif, suggesting specific regulatory functions different from those of the previously characterized MEKKs.