Ras, short for rat sarcoma, belongs to the monomer GTP binding protein with weak GTPase activity. Usually, Ras distributes on the cytoplasmic side of the plasma membrane and is inactive through the binding with GDP.
In the Ras signaling pathway, activated Ras further stimulates the phosphorylation of its substrate proteins, mediating many signaling pathways involved in various vital cellular processes.
The Ras signaling pathway is involved in many important cellular processes such as cell proliferation ＆survival, differentiation, apoptosis, cytoskeletal movement, protein transport ＆ secretion.
Normally, Ras combines with GDP and is in an inactive state. When Ras protein is released from Ras/GDP and binds to GTP, Ras is activated. Guanylate exchange factors (GEFs) (e.g. Sos) are stimuli for the activation of Ras. GAP (GTPase activating proteins) catalyzing the hydrolysis of GTP to GDP in Ras/GTP, deactivating Ras.
GEFs promote the release of GDP from Ras/GDP. Sos cannot bind directly to the receptor due to the lack of the SH2 domain. The adaptor protein Grb2 binds to the phosphotyrosine residue of the receptor via SH2 and then binds to Sos through SH3. Sos subsequently contacts Ras on the membrane to activate Ras. Or Ras is activated through the activation of RPTK by growth factors such as EGF, PDGF, and FGF.
Active Ras binds and activates Raf. Activated Raf phosphorylates and activates MEK1/2. MEK 1/2 phosphorylates ERK1/2 to activate it. Activation of ERK1/2 into the nucleus activates the expression of many downstream genes such as Elk-1, elf-4E to promote cell proliferation and differentiation.
In addition, activated Ras can directly bind and activate PI3K. Activation of PI3K converts PIP2 into PIP3. The second messenger PIP3 further stimulates PDK, which subsequently activates Akt, starting the PI3K-AKt signaling pathway that regulates cell proliferation.
RalGDS stimulates GDP to dissociate from the Ras-related RalA and RalB GTPases, which allows GTP binding and activation of the GTPases. RalBP can inhibit RacGTP and Cdc42 enzymes, and then regulate actin cytoskeleton remodeling and activate transcription factor NF-κβ through Rac/Cdc42. The process promotes the production of anti-apoptotic proteins to inhibit apoptosis.
The most common Ras gene mutation in tumors is the substitution of the 12th and 13th glycine or the 61st glutamine by other amino acid residues. AP is unable to hydrolyze GTP in mutant RAS. Without the help of GAP, the hydrolysis of GTP will be completely dependent on the GTPase of RAS itself, so the hydrolysis will last longer. This means that Ras/GTP cannot become Ras/GDP and is in a GTP-bound state for a long time, which causes excessive activation of the Ras-Raf-MEK-ERK pathway, resulting in excessive cell proliferation and tumorigenesis.
|ABL1||ABL1 Antibody||ABL1 Protein||ABL1 cDNA||ABL1 ELISA Kit|
|ABL2||ABL2 Antibody||ABL2 Protein||ABL2 cDNA||ABL2 ELISA Kit|
|AFDN||AFDN Antibody||AFDN Protein||AFDN cDNA||AFDN ELISA Kit|
|AKT1||AKT1 Antibody||AKT1 Protein||AKT1 cDNA||AKT1 ELISA Kit|
|AKT2||AKT2 Antibody||AKT2 Protein||AKT2 cDNA||AKT2 ELISA Kit|
|AKT3||AKT3 Antibody||AKT3 Protein||AKT3 cDNA||AKT3 ELISA Kit|
|ANGPT1||ANGPT1 Antibody||ANGPT1 Protein||ANGPT1 cDNA||ANGPT1 ELISA Kit|
|ANGPT2||ANGPT2 Antibody||ANGPT2 Protein||ANGPT2 cDNA||ANGPT2 ELISA Kit|
|ANGPT4||ANGPT4 Antibody||ANGPT4 Protein||ANGPT4 cDNA||ANGPT4 ELISA Kit|
|ARF6||ARF6 Antibody||ARF6 Protein||ARF6 cDNA||ARF6 ELISA Kit|
|BAD||BAD Antibody||BAD Protein||BAD cDNA||BAD ELISA Kit|
|BCL2L1||BCL2L1 Antibody||BCL2L1 Protein||BCL2L1 cDNA||BCL2L1 ELISA Kit|
|BDNF||BDNF Antibody||BDNF Protein||BDNF cDNA||BDNF ELISA Kit|
|BRAP||BRAP Antibody||BRAP Protein||BRAP cDNA||BRAP ELISA Kit|
|CALML3||CALML3 Antibody||CALML3 Protein||CALML3 cDNA||CALML3 ELISA Kit|
|CALML4||CALML4 Antibody||CALML4 Protein||CALML4 cDNA||CALML4 ELISA Kit|
|CALML5||CALML5 Antibody||CALML5 Protein||CALML5 cDNA||CALML5 ELISA Kit|
|CALML6||CALML6 Antibody||CALML6 Protein||CALML6 cDNA||CALML6 ELISA Kit|
|CDC42||CDC42 Antibody||CDC42 Protein||CDC42 cDNA||CDC42 ELISA Kit|
|CHUK||CHUK Antibody||CHUK Protein||CHUK cDNA||CHUK ELISA Kit|