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.
|GNGT2||GNGT2 Antibody||GNGT2 Protein||GNGT2 cDNA||GNGT2 ELISA Kit|
|GRB2||GRB2 Antibody||GRB2 Protein||GRB2 cDNA||GRB2 ELISA Kit|
|GRIN1||GRIN1 Antibody||GRIN1 Protein||GRIN1 cDNA||GRIN1 ELISA Kit|
|GRIN2A||GRIN2A Antibody||GRIN2A Protein||GRIN2A cDNA||GRIN2A ELISA Kit|
|GRIN2B||GRIN2B Antibody||GRIN2B Protein||GRIN2B cDNA||GRIN2B ELISA Kit|
|HGF||HGF Antibody||HGF Protein||HGF cDNA||HGF ELISA Kit|
|HRAS||HRAS Antibody||HRAS Protein||HRAS cDNA||HRAS ELISA Kit|
|HTR7||HTR7 Antibody||HTR7 Protein||HTR7 cDNA||HTR7 ELISA Kit|
|IGF1||IGF1 Antibody||IGF1 Protein||IGF1 cDNA||IGF1 ELISA Kit|
|IGF1R||IGF1R Antibody||IGF1R Protein||IGF1R cDNA||IGF1R ELISA Kit|
|IGF2||IGF2 Antibody||IGF2 Protein||IGF2 cDNA||IGF2 ELISA Kit|
|IKBKB||IKBKB Antibody||IKBKB Protein||IKBKB cDNA||IKBKB ELISA Kit|
|IKBKG||IKBKG Antibody||IKBKG Protein||IKBKG cDNA||IKBKG ELISA Kit|
|INS||INS Antibody||INS Protein||INS cDNA||INS ELISA Kit|
|INSR||INSR Antibody||INSR Protein||INSR cDNA||INSR ELISA Kit|
|KDR||KDR Antibody||KDR Protein||KDR cDNA||KDR ELISA Kit|
|KIT||KIT Antibody||KIT Protein||KIT cDNA||KIT ELISA Kit|
|KITLG||KITLG Antibody||KITLG Protein||KITLG cDNA||KITLG ELISA Kit|
|KRAS||KRAS Antibody||KRAS Protein||KRAS cDNA||KRAS ELISA Kit|
|KSR1||KSR1 Antibody||KSR1 Protein||KSR1 cDNA||KSR1 ELISA Kit|