Activation of receptor tyrosine kinase is a rather complicated process. Most receptors must first form a dimer from two monomers, then phosphorylate at the tail of the intracellular domain, and then assemble a signal transduction complex in the intracellular domain of the dimer.

What are the main types of RTK concentration?

Epidermal growth factor receptor, platelet growth factor receptor, insulin and insulin-like growth factor-1? Receptor, etc

Insulin receptor signal transduction pathway

Insulin receptor (insulin? Receptor) is a tetramer, which is composed of two α subunits and two β subunits connected by disulfide bonds.

Activate?

When insulin binds to the α subunit of the receptor and changes the configuration of the β subunit, tyrosine protein kinase is activated, which can catalyze two reactions: ① phosphorylation of tyrosine residues at the β subunit site in the tetramer complex, which is called autophosphorylation; ② Insulin receptor substrate (insulin? Receptors? More than a dozen tyrosine residues (IRSs) on the substrate are phosphorylated, and the phosphorylated IRSs can bind to those protein with SH2 domain, causing further reactions.

Insulin receptor is a tetramer composed of two α subunits and two β subunits. The combination of insulin and α subunit causes the configuration change of β subunit and activates tyrosine kinase of β subunit. The activated β subunit phosphorylates tyrosine located in the cytoplasmic domain of the receptor and various IRS of the receptor.

Signal transduction mechanism?

Once the insulin receptor is activated and the IRSs is phosphorylated, the phosphorylated IRSs can be used as an anchor point to anchor many different protein with SH2 domain. These ankyrin can activate different signal transduction pathways, thus transmitting extracellular signals received by insulin receptors to cells through different channels.

The activated insulin receptor phosphorylates IRSs, and the phosphorylated IRSs can activate PI(3)K, PI-PLC and Ras pathways.

Epidermal growth factor receptor signal transduction pathway

Epidermal growth factor? Grow up? Factor,? EGF receptor is a well-studied tyrosine kinase receptor, which exists in the plasma membrane of specific target cells, regulates different functions, including cell growth, proliferation and differentiation, and is related to the occurrence of tumors.

Receptor structure?

EGF receptor is a glycoprotein, which consists of three parts: ① There are 62/kloc-0 amino acid residues in extracellular domain, which are rich in cysteine. And multiple pairs of disulfide bonds are formed. Glycosyl is the binding site of EGF. ② The transmembrane region consists of 23 amino acid residues; ③ Cytoplasmic domain, consisting of 542 amino acid residues, contains inactive tyrosine kinase and several tyrosine phosphorylation sites.

Receptor activation?

When EGF binds to the binding site of the extracellular domain of the receptor, the receptor is activated, resulting in the formation of dimer of two EGF receptor monomers. Activate tyrosine kinase in cytoplasm to make tyrosine self-phosphorylate. There are five major phosphorylated tyrosine sites on EGF receptor, which can bind to several different protein and cause different signal responses in cells.

Cascade amplification?

In most cases, the phosphorylated tyrosine site of EGF receptor interacts with the SH2 domain of the target protein (enzyme), which activates the target protein (enzyme) and causes cell reaction. For example, PIP2 kinase is activated through the interaction between SH2 and tyrosine sites phosphorylated by EGF receptor, and the activated PIP2 kinase phosphorylates membrane lipid -PIP2. In addition, the phosphorylated tyrosine site can also interact with phospholipase Cγ with SH2 domain to activate phospholipase Cγ. Activated phospholipase Cγ can hydrolyze PIP2 in plasma membrane into IP3 and DAG, causing signal transduction similar to phosphoinositide -G protein coupling system.

Ras？ The Activation of protein

Protooncogene? C-ras expression product? Ras protein is a well-studied signal transduction pathway, which is related to insulin receptor and EGF receptor.

Ras protein (Ras? Protein)? Ras is mouse sarcoma (mouse? Sarcoma, Ras). Ras protein is the expression product of proto-oncogene c-ras, and its relative molecular weight is 2 1kDa. GTP binding protein, with weak? Gtpase activity. Its activities are regulated by combining with GTP or GDP.

The activity of Ras protein is controlled by GEF and GAP. GEF activates Ras, while GAP inhibits Ras activity.

Activation of Ras protein

When EGF activates its receptor, the cytoplasmic domain of the receptor is phosphorylated, and the new phosphorylation site serves as the binding site of Grb2-Sos protein. After Grb2-Sos protein binds to the phosphorylation site of receptor, Sos protein is activated, and the activated Sos protein promotes the relationship between GDP and Ras protein. Exchange GTP, thus activating Ras protein.

Ras protein can also be activated by insulin receptor, and its activation mechanism is slightly different. In the insulin receptor pathway, Grb2-Sos protein cannot directly bind to the phosphotyrosine site of the receptor cytoplasmic domain, but binds to the insulin receptor substrate Shc to form the Shc-Grb2-Sos protein complex.

Ras signal cascade amplification

After Ras protein is activated, signal transduction is carried out through kinase cascade system (attached figure)

It may feel a little irrelevant.