Signal pathway is the phenomenon that the signal transmits a kind of information from the outside of the cell to the inside of the cell when there is a certain reaction in the cell, according to which the cell has to react. The idea of Signal pathway dates back to 1972. But at that time, it was called signal transmission. The concept of signal transduction was widely used by M. Rodbell in a review in 1980.
Do you know Toll and Imd Signaling Pathway?
Inflammation induced by members of the TLR family (except TLR3) goes through a classic signaling pathway. This pathway originated from the Toll/IL-1 receptor homologous region (TIR), which is an intracellular conserved sequence of TLRs. TIR activates intracellular signaling mediators-interleukin-1 receptor-associated protein kinase (IL-1R associated kinase, IRAK) IRAK-1 and IRAK-4, TNFR-associated factor 6 (TRAF-6). Mitogen-activated protein kinase (mitogen activated protein kinase, MAPK and I κ B kinase, I κ K), NF-κ B) induces the expression of inflammatory factors.
The signal molecules involved in this signal transduction include:CD14，MD-2，TRAM，TRIF，TIRAP，MyD88，TLR1，TLR2，TLR3，TLR4，TLR5，TLR6，TLR7，TLR8，TLR9，IRAK-1，IRAK-2，IRAK-4，IRAK-M，TRAF6，TRIAD3A，ST2L，SOCS1，RIG-I，FADD，TOLLIP，RIP1，A20，UEV1A， Ubc13，ECSIT， MEKK-1， TAK1，TBK1， MKK3/6， p38， TAB1/2， MKK4/7， JNK， IKKα， IKKβ， IKKγ， IKKε，NEMO， IκBα， NF-κB， p65/RelA， Casp-8， IRF-3，IRF-7，MAVS and so on.
Do you know NOD-like Receptor Signaling Pathway?
By activating innate and adaptive immunity, microbes initiate a series of defensive processes. The congenital immune system consists of immune and non-immune cells expressed on the sensor or pattern recognition receptor (PRRS) and associated molecular patterns (PAMPS) from different pathogens. PAMPS recognizes inflammatory cytokines and type I interferons that trigger antimicrobial effects through induction. Toll like receptors, NOD receptors, RIG-I receptors and DNA sensors have been well studied. Let’s see what the signaling pathways of NOD receptors look like.
NOD like receptor is widely found in the cytoplasm of human cells whose corresponding ligand can activate NF-K B (NOD1 and NOD2) signaling pathway and activate Caspa se-1 to promote the production of IL-1B and IL-18, thus initiating innate and acquired immunity. NOD protein is the pattern recognition receptor in the plasma and its structure is as follows:
- 1.The central nucleotide binding oligodepolymerization region (NACHT) is a common structure of the NLRs family, which is very important for the oligomerization and activation of NLRs.
- 2.The N-terminal effect binding region is the domain of the interaction between N-terminal diWhite and protein.
- 3.The repeat sequence (LRRs), which is rich in leucine at the C-terminal, can recognize the receptor and the mutations of NOD2 and N-LRP3 in the NOD family can cause inflammation. So at present, the most studied is the NOD-like molecule. NOD1 and NOD2 can recognize different degradation products of bacterial peptidoglycan, and then activate two signal pathways, MAPK and NFBK, by RIP2 kinase (RICK), with the same CARD structure in its CARD oligoset.
Do you know RIG-I-like Receptor Signaling Pathway?
RIG-I is retinoic acid to induce gene protein I (RIG-I). RIG is a cellular receptor that recognizes viral double-stranded RNA and is a member of the RNA helicase family of DexD/H boxes. The C-terminal of RIG-I is a helical domain, which can be combined with synthetic double-stranded RNA and viral double-stranded RNA, and can be solved by ATP enzyme dependent way. The N-terminal is two series of cysteinase recruitment domain (CARD). RIG-I can recognize the RNA component of the virus and transmit signals by its own CARD interacting with the downstream signal molecule MAVS CARD. It activates the transcription factors IRF-3 and NF-κB into the nucleus and induces the expression of interferon B. In order to initiate the innate immune response and regulate the subsequent acquired immune response, it can enhance the ability of the body to resist the virus. In addition, in recent years, two viral RNA recognition proteins, MDA5 and LGP2, have been found to be similar in sequence and function to RIG-I too.