SAPK/JNK signal pathway map

c-Jun N-terminal kinase (JNK), also known as stress-activated protein kinase (SAPK), is another subclass of MAPK in mammalian cells. At present, 10 JNK isoforms have been cloned from mature human brain cells, which are encoded by JNK1, JNK2 and JNK3 genes, respectively [3], JNK1 with a molecular weight of 46,000 and JNK2 with a molecular weight of 55,000 are widely used in various tissue cells. Expression, while JNK3 is selectively expressed in brain cells.

JNK/SAPK signaling pathway can be conjugated by stress (such as UV, heat shock, hypertonic stimulation and protein synthesis inhibitors), cytokines (TNFα, IL-1), growth factors (EGF) and certain G proteins. Receptor activation. External stimuli can activate JNK through two pathways, Ras-dependent or non-Ras-dependent. Rho, a member of the small-molecule G-protein Ras superfamily, may also be the upstream signal of JNK activation [4]. The role of Rho protein Rac and cdc42 may be The p21-activated silk/threonine kinase PAK binds to its own phosphorylation and is activated, while the activated PAK further activates JNK. Studies have confirmed that the bispecific kinase JNK Kinase (JNKK) is an upstream activator of JNK/SAPK, including MKK4 (JNKK1) and MKK7 (JNKK2), of which MKK7/JNKK2 can specifically activate JNK[5], while MKK4 JNK1 and p38 can be activated at the same time. The upstream activator of JNKK is MEKK, which activates MEK when overexpressed in vitro, but MEKK1 phosphorylates MKK4 highly selectively in vivo, thereby activating JNK [6]. MEKK2 also activates JNK and p38 via MKK4. After the upstream signal is activated, JNK/SAPK can further phosphorylate the serine residues at the amino terminal 63 and 73 of the nuclear transcription factor c-Jun, thereby activating c-Jun and enhancing its transcriptional activity [7]. Phosphorylation of the c-Jun amino terminus also promotes the formation of c-Jun/c-Fos heterodimers and c-Jun homodimers, which can bind to AP-1 sites in many gene promoter regions. Increase the transcriptional activity of a particular gene. In addition, activation of JNK/SAPK also phosphorylates the transcription factors Elk-1 and ATF2 and enhances their transcriptional activity.

The signal molecules involved in this signal transduction mainly include:

CrkL, Shc, GRB2, JNK, JNK1, JNK2, JNK3, MKK4, MKK7, IRS-1, c-Abl, Bax, CrkII, TAK1, ASK1, MAPKKKs, HPK1, GCK, MEKK1, MEKK4, MLK2, MLK3, DLK, TpI-2, TAO1, TAO2, PI3Kγ, c-Jun, SOS, Ras, TRAF2, Daxx, POSH, MLKs, MKPs, NFATc1, Gα12, Gβγ, JIP1, JIP2, JIP3, ATF-2, Elk-1, Smad4, P53, NFAT4, Stat3, Rac, Cdc42, Rho, HSF1, Gα13, 14-3-3, etc.

Click on the signal molecule in the figure to view detailed pathway maps and products (inhibitors, antibodies, phosphorylated antibodies, assay kits, recombinant proteins, etc.):