scholarly journals Nitration-induced ubiquitination and degradation control quality of ERK1

2019 ◽  
Vol 476 (13) ◽  
pp. 1911-1926 ◽  
Author(s):  
Yuanya Zhang ◽  
Xiahe Huang ◽  
Jinlong Wang ◽  
Xiaorong Wang ◽  
Xiaofei Liu ◽  
...  
Keyword(s):  
Quality Control ◽  
Wide Spectrum ◽  
Control Program ◽  
Stress Conditions ◽  
Mitogen Activated Protein Kinase ◽  
General Mechanism ◽  
Quality Control Program ◽  
Interacting Protein ◽  
Spatiotemporal Regulation ◽  
Mitogen Activated Protein

Abstract The mitogen-activated protein kinase ERK1/2 (ERKs, extracellular-regulated protein kinases) plays important roles in a wide spectrum of cellular processes and have been implicated in many disease states. The spatiotemporal regulation of ERK activity has been extensively studied. However, scarce information has been available regarding the quality control of the kinases to scavenge malfunctioning ERKs. Using site-specific mutagenesis and mass spectrometry, we found that the disruption of the conserved H-bond between Y210 and E237 of ERK1 through point mutation at or naturally occurring nitration on Y210 initiates a quality control program dependent on chaperon systems and CHIP (C-terminal of Hsp70-interacting protein)-mediated ubiquitination and degradation. The H-bond is also important for the quality control of ERK2, but through a distinct mechanism. These findings clearly demonstrate how malfunctioning ERKs are eliminated when cells are in certain stress conditions or unhealthy states, and could represent a general mechanism for scavenging malfunctioning kinases in stress conditions.

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.

Lung Function Test for Workers and its Quality Control Program

1994 ◽  
Vol 6 (2) ◽  
pp. 187
Author(s):  
Jung Keun Choi ◽  
Mi A Son ◽  
Hyun Kyung Kim ◽  
Domyung Paek ◽  
Byung Soon Choi
Keyword(s):  
Quality Control ◽  
Lung Function ◽  
Control Program ◽  
Lung Function Test ◽  
Quality Control Program ◽  
Function Test

A Quality Control Program for Acute Pain Management in Out-of-Hospital Critical Care Medicine

1999 ◽  
Vol 34 (6) ◽  
pp. 738-744 ◽  
Author(s):  
Agnès Ricard-Hibon ◽  
Charlotte Chollet ◽  
Sylvie Saada ◽  
Bertrand Loridant ◽  
Jean Marty
Keyword(s):  
Quality Control ◽  
Critical Care ◽  
Pain Management ◽  
Acute Pain ◽  
Control Program ◽  
Critical Care Medicine ◽  
Acute Pain Management ◽  
Quality Control Program

scholarly journals Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 711-719 ◽  
Author(s):  
Munkhuu Bayarsaikhan ◽  
Akiko Shiratsuchi ◽  
Davaakhuu Gantulga ◽  
Yoshinobu Nakanishi ◽  
Katsuji Yoshioka
Keyword(s):  
Protein Kinase ◽  
Western Blotting ◽  
Cell Types ◽  
Mapk Signaling ◽  
Scaffold Protein ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Early Postnatal Development ◽  
Mitogen Activated Protein ◽  
Signaling Modules

Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal transduction pathways mediate the efficient and specific activation of the relevant MAPK signaling modules. Previously, our group and others have identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its expression during development has not been investigated. In addition, it is unknown which types of cells in the testis express the scaffold protein. Here, we examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6 weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously expressed JSAP1 and a structurally related protein, and by antigen-absorption experiments. The immunohistochemical analyses with the specific antibody showed that the JSAP1 protein was selectively expressed in the spermatogonia and spermatocytes, but not in other cell types, including spermatids and somatic cells, during development. However, not all spermatogonia and spermatocytes were immunopositive either, especially in the 12-week-old mouse testis. Furthermore, we found by Western blotting that the expression levels of JSAP1 protein vary during development; there is high expression until 6 weeks after birth, which approximately corresponds to the end of the first wave of spermatogenesis. Collectively, these results suggest that JSAP1 function may be important in spermatogenic cells during early postnatal development.

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