MAPK Signaling Pathway

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway is a conserved and intricate cellular communication network that plays a pivotal role in transducing extracellular signals into various cellular responses. This pathway is crucial for regulating fundamental processes such as cell proliferation, differentiation, survival, and apoptosis. Three MAPK families have been characterized in mammalian cells: classical MAPK-ERK, JNK/SAPK, and p38 kinase. Get products for the entire MAPK signaling pathway. In many cancers, these pathway members are either deregulated or mutated. Download the poster, which provides a detailed overview of the three MAPK signaling cascades.

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MAPK-ERK Pathway

The Mitogen-Activated Protein Kinase-Extracellular Signal-Regulated Kinase (MAPK-ERK) pathway represents a canonical signaling cascade crucial in orchestrating diverse cellular processes. The binding of extracellular ligands initiates this pathway, predominantly growth factors or hormones, to cell surface receptors such as receptor tyrosine kinases (RTKs), which play a pivotal role in transducing extracellular signals to intracellular responses.

Upon ligand binding, receptor activation ensues, leading to autophosphorylation and the recruitment of adaptor proteins. Subsequently, these adaptors facilitate the activation of Ras, a small GTPase, by instigating the exchange of GDP for GTP. Activated Ras, in turn, serves as a key node, initiating a sequential kinase cascade. The Raf kinases, comprising A-Raf, B-Raf, and C-Raf isoforms, become activated through association with GTP-bound Ras. Activated Raf kinases phosphorylate and activate Mitogen-Activated Protein Kinase Kinase (MEK), a dual-specificity kinase with the ability to phosphorylate extracellular signal-regulated kinases (ERKs) on tyrosine and threonine residues.

ERKs, notably ERK1 and ERK2, subsequently translocate to the nucleus, where they exert their regulatory influence by phosphorylating an array of transcription factors and other nuclear substrates. This nuclear signaling cascade culminates in alterations of gene expression profiles, thereby modulating cellular responses, including but not limited to cell proliferation, differentiation, survival, and apoptosis.

The hyperactivation of the MAPK-ERK pathway is a prevalent phenomenon across a myriad of tumors, where a subset of its constituent elements has been recognized as potent oncogenes. The delineation and characterization of these oncogenic components have engendered a profound intrigue. Consequently, the prospect of targeting this intricate signaling cascade has emerged as a compelling and promising therapeutic strategy in cancer research. Empower your studies of these mutated genes with OriGene’s TrueMAB® antibodies developed for specificity.

Antibodies for Mutated Genes in MAPK Pathway


Mapk Erksignaling Pathway

MAPK-JNK Pathway

The Mitogen-Activated Protein Kinase c-Jun N-terminal Kinase (MAPK-JNK) signaling pathway represents a specialized arm within the broader MAPK cascade, specifically tailored to respond to a spectrum of stress stimuli. The JNK pathway and its downstream substrates, initially identified as stress-activated protein kinases (SAPKs), have emerged as pivotal players in cellular responses, particularly in inflammation and apoptosis induction.

The MAPK-JNK pathway comprises three genes (Jnk1, Jnk2, and Jnk3) in mammals, with Jnk1 and Jnk2 exhibiting broad expression profiles, and Jnk3 specifically expressed in the brain, heart, and testis, JNKs are activated by various stressors, including UV irradiation and oxidative stress, eliciting apoptotic or growth inhibitory responses. The upstream kinases of the JNK pathway, namely MAP2Ks MKK4 and MKK7, are activated by distinct MAP3Ks.

Upon activation, JNKs translocate from the cytoplasm to the nucleus. The primary downstream target of JNK is the transcription factor c-Jun, which undergoes nuclear translocation following JNK-mediated phosphorylation. Notably, c-Jun regulates the expression of genes with pro-apoptotic or anti-apoptotic functions, such as Bax (Bcl2-associated X protein) and Bcl-2 (B-cell lymphoma 2). JNK activation involves the phosphorylation of serine residues 63 and 73 at the c-Jun N-terminal, activating c-Jun and enhancing its transcriptional activity. Additionally, there is evidence suggesting that the association between JNK and c-Jun serves not only to activate but also to stabilize c-Jun. This multifaceted interplay between JNK and its downstream substrates highlights the intricate regulatory mechanisms that govern cellular responses to stress and inflammation. On the one hand, it promotes cell survival and proliferation; on the other, it causes cell death.

Deciphering the pathological role of JNK signaling has proven challenging, given its dual nature. Nevertheless, through sequencing analyses of cancer genomes, a distinctive clustering of multiple genes within the JNK pathway has been unveiled.

Antibodies for Mutated Genes in MAPK Pathway


MAPK-JNK Signaling Pathway

MAPK-P38 Pathway

A diverse range of extracellular stimuli across various organisms triggers the activation of the p38 pathway. Mammalian p38 isoforms respond to extracellular stimuli like UV light, heat, osmotic shock, inflammatory cytokines, and growth factors

p38 kinases, like all MAP kinases, are activated by MAP kinase kinases (MKKs). Selective activation of distinct p38 isoforms (α, β, γ, and δ) by specific MKKs has been observed. MKK3 and MKK6 are the main MAPKKs activating p38, with differences in their ability to activate specific p38 isoforms. MKK4, an upstream kinase of JNK, can also contribute to activating p38α and p38δ in particular cell types.

Besides MKK-dependent activation, a MAPKK-independent mechanism involves TAB1, leading to the autophosphorylation of p38α after the interaction. The activation of p38 in response to extracellular stimuli involves a range of MAP3Ks (MKK kinases). TAK1, ASK1/MAPKKK5, DLK/MUK/ZPK, and MEKK4 are MAP3Ks participating in p38 activation. Additionally, low molecular weight GTP-binding proteins in the Rho family, such as Rac1 and Cdc42, contribute to p38 activation upstream of MAPK kinases. p38 MAPK is involved in regulation of MAPKAPK-2 (MK2), MAPKAPK-3 (MK3), and several transcription factors including ATF-2,Stat3, Elk-1 etc.

The role of p38 MAPK is to activate cellular responses by modulating a wide variety of targets, including TP53, an epitome of tumor suppressor. Studies are still going on p38MAPK inhibitors to evaluate their efficacy as therapeutic targets. Some essential genes that are being studied are:

Key Markers:

IL-24 P53 P38 MEK4 MKK6

P38-MAPK Signaling Pathway

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