JNK SIGNALING PATHWAY, A STRESS ACTIVATED PROTEIN KINASES

The JNK signalling pathway (c-Jun N-terminal kinase) is a conserved response to a wide range of internal and external cellular stress stimuli. A number of essential regulatory mechanisms involve it during development and adulthood to maintain tissue homeostasis. This regulatory mechanisms include the regulation of apoptosis, growth, proliferation, differentiation, migration, invasion, inflammatory response, autophagy, innate and adaptive immune responses ... ^(1,3,4) .

JNK-pathway, stress-activated protein kinases (SAPK)

c-Jun N-terminal kinase (JNK) signaling pathway activation. ⁽⁴⁾ .

c-Jun N-terminal kinase is a serine/threonine kinase encoded by three genes. These genes are JNK1, JNK2 and JNK3. Respectively encode three different isoforms mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 9 (MAPK9) and mitogen-activated protein kinase 10 (MAPK10).

It is part of the canonical mitogen activated protein kinase (MAPK) family. These proteins are highly responsive to a diverse array of stress stimuli. This includes UV radiation, bacterial and viral infections, heat shock, and osmotic and genotoxic stresses.

c-Jun N-terminal kinases JNKs also known as stress-activated protein kinases (SAPK). This is due to its important role in the stress response.

Activation of the c-Jun N-terminal kinase pathway depends largely on the context and duration of activation. Transient activation of JNK pathway could result in proliferation, whereas prolonged activation could trigger cell death.

In response to environmental stresses, growth factor, and cytokines, JNKKKs (JNK kinase kinases) like ASK1 phosphorylates JNKKs (JNK kinases). Then, the JNKKs activate JNK. Specifically, upstream MAPK2K (MKK4 and MKK7) activates JNK. This via phosphorylation of the threonine and tyrosine residues of the conserved ThrProTyr (TPY) motif.

Upon activation, JNK phosphorylates downstream target proteins. Among them activator of transcription factor-1 (AP1) protein family, activating transcription factors (ATF), and (ETS protein Like- 1) Elk1.^(3,4).

RELATIONSHIP BETWEEN C-JUN N-TERMINAL KINASE PATHWAY AND DISEASES

The c-Jun N-terminal kinase pathway play a key role in renewal and in many diseases. Among them, tumorigenesis such as glioblastoma, ovarian cancer, melanoma, basal cell and squamous cell carcinoma. In addition to neurodegenerative diseases like Alzheimer, Parkinson, Huntington, and muscle wasting in cancer cachexia, psoriasis and dermal fibrosis....

There is evidence to suggest that this signaling pathway functions as both a tumor suppressor and a cancer promoter. This pathway may thus be a viable target for molecular cancer therapy because of its complex impact on cancer ^(2,3,4).

(1) de Los Reyes Corrales T et al. JNK Pathway in CNS Pathologies. Int J Mol Sci. (2021);22(8):3883.

(2) Mulder SE et al. JNK signaling contributes to skeletal muscle wasting and protein turnover in pancreatic cancer cachexia. Cancer Lett. (2020);491:70-77.

(3) Dou Y et al. The Jun N-terminal kinases signaling pathway plays a "seesaw" role in ovarian carcinoma: a molecular aspect. J Ovarian Res. (2019);12(1):99.

(4) Hammouda MB et al. The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer . Cells. (2020);9(4):857.

JNK SIGNALING PATHWAY BIOMARKER LIST

You can custom your own SignArrays® with the genes of interest of your choice, according to your project, you just have to download and complete our Personalized SignArrays® information file and send it at [email protected]

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human Signaling

Signaling Pathways	Product ref	Informations
JNK Signaling Pathway	JNK1H1	List infos

Species : Mus musculus (mouse)

Mouse Signaling

Signaling Pathways	Product ref	Informations
JNK Signaling Pathway	*******	List In progress...

Species : Rattus norvegicus (rat)

Rat Signaling

Signaling Pathways	Product ref	Informations
JNK Signaling Pathway	*******	List In progress...

Species : Sus Scrofa (Pig)

Pig Signaling

Signaling Pathways	Product ref	Informations
JNK Signaling Pathway	*******	List In progress...

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