Search results for SOS1

Showing 15 results out of 251

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Reaction (5 results from a total of 141)

Identifier: R-HSA-8851899
Species: Homo sapiens
Compartment: cytosol, plasma membrane
SOS1, recruited to activated MET receptor via interaction of GRB2 with phosphorylated SHC1-2, catalyzes guanyl nucleotide exchange on RAS from GDP to GTP, resulting in RAS activation (Pelicci et al. 1995).
Identifier: R-HSA-9664991
Species: Homo sapiens
Compartment: cytosol, plasma membrane
For the following ERBB2 KD mutants that were shown to activate RAS/RAF/MAPK signaling, it is assumed that they, like phosphorylated heterodimers of the wild type ERBB2, bind to and phosphorylate SHC1, leading to recruitment of the GRB2:SOS1 complex and activating guanyl-nucleotide exchange on RAS:

ERBB2 L755P (Kancha et al. 2011);
ERBB2 L755S (Trowe et al. 2008, Kancha et al. 2011, Bose et al. 2013, Cocco et al. 2018);
ERBB2 I767M (Ng et al. 2015);
ERBB2 D769H (Bose et al. 2013);
ERBB2 V777L (Kancha et al. 2011, Bose et al. 2013);
ERBB2 G778_P780dup (Suzawa et al. 2016);
ERBB2 T798I (Hanker et al. 2017);
ERBB2 T798M (Kancha et al. 2011, Rexer et al. 2013);
ERBB2 V842I (Bose et al. 2013);
ERBB2 T862A (Kancha et al. 2011);
ERBB2 L869R (Hanker et al. 2017);
ERBB2 H878Y (Kancha et al. 2011, Hu, Hu et al. 2015, Hu, Wan et al. 2015);
ERBB2 R896C (Bose et al. 2013);
ERBB2 L755_T759del (Bose et al. 2013);
ERBB2 G776S (Fan et al. 2008);
ERBB2 Y772_A775dup (Wang et al. 2006);

Activation of RAS/RAF/MAPK signaling downstream of the following ERBB2 KD cancer mutants has not been studied and they are annotated as candidates:

ERBB2 L755M
ERBB2 L755W
ERBB2 D769Y
ERBB2 D769N
ERBB2 V777M
ERBB2 V777E
ERBB2 T733I
ERBB2 V842E
ERBB2 L869Q
ERBB2 H878R
ERBB2 R896H
ERBB2 G776C
ERBB2 G776L
ERBB2 G776V
Identifier: R-HSA-9665700
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Activation of downstream RAS signaling was shown for ERBB2 S653C (de Martino et al. 2014) and ERBB2 R678Q (Bose et al. 2013, de Martino et al. 2014) through activating tyrosine phosphorylation on ERKs (MAPK1 and MAPK3) and SHC1. It is assumed that heterodimers of ERBB2 TMD/JMD mutants, like the wild type ERBB2 heterodimers, bind to and phosphorylate SHC1, leading to the recruitment of the GRB2:SOS1 complex and activation of RAS through guanyl nucleotide exchange.
Identifier: R-NUL-1250472
Species: Rattus norvegicus, Mus musculus, Homo sapiens
Compartment: plasma membrane, cytosol
Sos1 bound to exogenously expressed human GRB2 in complex with phosphorylated mouse Shc1 and phosphorylated rat oncoprotein Erbb2mut catalyzes guanyl-nucleotide exchange on endogenous Ras in mouse fibroblasts (Xie et al. 1995).
Identifier: R-HSA-9634418
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Based on activation of RAS signaling by autophosphorylated ERBB2 homodimers, as well as binding of GRB2 and SHC1 to ERBB2 homodimers (Pickl and Ries 2009), it is assumed that SOS1, recruited to ERBB2 homodimers through GRB2, mediates GDP to GTP exchange on RAS protein family, resulting in formation of the active RAS:GTP complex.

Complex (5 results from a total of 84)

Identifier: R-HSA-205202
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5686070
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9607300
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5654287
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-109798
Species: Homo sapiens
Compartment: cytosol

Pathway (5 results from a total of 18)

Identifier: R-HSA-912526
Species: Homo sapiens
Compartment: plasma membrane
Phosphorylation of Shc at three tyrosine residues, 239, 240 (Gotoh et al. 1996) and 317 (Salcini et al. 1994) involves unidentified tyrosine kinases presumed to be part of the activated receptor complex. These phosphorylated tyrosines subsequently bind SH2 signaling proteins such as Grb2, Gab2 and SHIP that are involved in the regulation of different signaling pathways. Grb2 can associate with the guanosine diphosphate-guanosine triphosphate exchange factor Sos1, leading to Ras activation and regulation of cell proliferation. Downstream signals are mediated via the Raf-MEK-Erk pathway.Grb2 can also associate through Gab2 with PI3K and with SHIP.

Figure reproduced from Gu, H. et al. 2000. Mol. Cell. Biol. 20(19):7109-7120
Copyright American Society for Microbiology. All Rights Reserved.
Identifier: R-HSA-5654699
Species: Homo sapiens
Compartment: plasma membrane
The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR.
Identifier: R-HSA-5654719
Species: Homo sapiens
Compartment: plasma membrane
The exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction with the receptor has not been demonstrated. Co-precipitation of p46 and p52 with the FGFR2 IIIc receptor has been reported, but this interaction is thought to be indirect, possibly mediated by SRC. Consistent with this, co-precipitation of SHC1 and FGFR1 IIIc is seen in mammalian cells expressing v-SRC. The p66 isoform of SHC1 has also been co-precipitated with FGFR3, but this occurs independently of receptor stimulation, and the p66 isoform not been shown to undergo FGF-dependent phosphorylation. SHC1 has been shown to associate with GRB2 and SOS1 in response to FGF stimulation, suggesting that the recruitment of SHC1 may contribute to activation of the MAPK cascade downstream of FGFR.
Identifier: R-HSA-9680350
Species: Homo sapiens
Colony stimulating factor-1 (CSF1, CSF-1, also called macrophage colony stimulating factor, M-CSF) is a disulfide-linked dimer that stimulates the proliferation and differentiation of mononuclear phagocytes and the survival, proliferation, motility, and anti-inflammatory activity of macrophages (reviewed in Mouchemore et al. 2012, Stanley and Chitu 2014, Ushach and Zlotnik 2016, Dwyer et al. 2017 and inferred from mouse homologs in Caescu et al. 2015). The unliganded CSF1 receptor, CSF1R (CSF-1R) is either clustered or undergoing rapid dimer-monomer transitions at the cell surface (Li and Stanley 1991). The CSF1 dimer initially binds the D2 and D3 extracellular domains of a monomer of CSF1R (Wang et al. 1993, Chihara et al. 2010, Ma et al. 2012, Felix et al. 2015, and inferred from mouse homologs). A second monomer of CSF1R then binds the CSF1:CSF1R complex and the resulting dimerization of CSF1R activates its kinase activity (Elegheert et al. 2011, Felix et al. 2015, and inferred from mouse homologs). CSF1R initially trans-autophosphorylates tyrosine-561 in the juxtamembrane domain, relieving negative autoinhibition of kinase activity, resulting in the trans-autophosphorylation of 7 more tyrosine residues in its cytoplasmic domain (Rohrschneider et al. 1997, Chihara et al. 2010, and inferred from mouse homologs in Xiong et al. 2011).
The PIK3R1 (p85alpha) regulatory subunit of phosphatidylinositol 3-kinase (PI3K) binds phosphotyrosine-723 of CSF1R, phosphorylated SRC binds phosphotyrosine-561 of CSF1R, phosphorylated CBL binds CSF1R associated with SHC, and GRB2:SOS binds CSF1R (Saleem et al. 1995, and inferred from mouse homologs). The resulting activation of the catalytic subunit of PI3K (PIK2CA,B,G) produces phosphatidylinositol 3,4,5-trisphosphate which recruits effectors containing pleckstrin homology domains (PH domains) such as PKB (also called Akt) to the plasma membrane. Pathways activated by PI3K appear to both enhance proliferation, survival, and migration of macrophages (reviewed in Dwyer et al. 2017) and, via induction of miR21, suppress the inflammatory response by targeting mRNAs encoding multiple proinflammatory molecules.
Phospholipase C gamma2 (PLCG2) binds phosphotyrosine-723 of CSF1R, hydrolyzes phosphatidylcholine to yield choline phosphate (phosphocholine) and diacylglycerol, and promotes survival and differentiation of macrophages via PKCdelta (PRKCD) (inferred from mouse homologs).
GRB2 bound to SOS1 (GRB2:SOS1) transiently interacts with phosphotyrosine-699 of CSF1R. SOS1 promotes the exchange of GDP for GTP by KRAS, activating the RAS-RAF-ERK1,2 pathway that causes proliferation of macrophage precursors (inferred from mouse homologs). CBL transiently associates with and ubiquitinates the CSF1R, then is deubiquitinated and returned to the cytoplasm (inferred from mouse homologs).
Phosphorylated CSF1R also recruits STAT1 and STAT3, which are then phosphorylated (inferred from mouse homologs). The role of phosphorylated STAT1,3 in signaling by CSF1R is incompletely characterized.
CSF1R is a target for therapeutics, such as imatinib (reviewed in Kumari et al. 2018).
Identifier: R-HSA-1839117
Species: Homo sapiens
Compartment: cytosol
8p11 myeloproliferative syndrome (EMS) is an aggressive disorder that is associated with a translocation event at the FGFR1 gene on chromosome 8p11. Typical symptoms upon diagnosis include eosinophilia and associated T-cell lymphoblastic lymphoma; the disease rapidly advances to acute leukemia, usually of myeloid lineage. At present the only effective treatment is allogenic stem cell transplantation (reviewed in Jackson, 2010).

At the molecular level, EMS appears to be caused by translocation events on chromosome 8 that create gene fusions between the intracellular domain of FGFR1 and an N-terminal partner gene that encodes a dimerization domain. The resulting fusion protein dimerizes in a ligand-independent fashion based the N-terminal domain provided by the partner protein and stimulates constititutive downstream FGFR1 signaling without altering the intrisic kinase activity of the receptor. To date, 11 partner genes have been identified: ZMYM2, FGFR1OP, FGFR1OP2, HERVK, TRIM24, CUX1, BCR, CEP110, LRRFIP1, MYO18A and CPSF6, although not all have been functionally characterized (reviewed in Jackson, 2010, Turner and Grose, 2010; Wesche, 2011).
Where examined, cell lines carrying FGFR1 fusion genes have been shown to be transforming and to support IL3-independent proliferation through anti-apoptotic, prosurvival pathways(Lelievre, 2008; Ollendorff, 1999; Chase, 2007; Guasch, 2001; Wasag 2011; Roumiantsev, 2004; Demiroglu, 2001; Smedley, 1999). Signaling appears to occur predominantly through PLCgamma, PI3K and STAT signaling, with a more minor contribution from MAPK activation. Because the fusion proteins lack the FRS2-binding site, the mechanism of MAPK activation is unclear. Recruitment of GRB2:SOS1 through recruitment of SHC is one possibility (Guasch, 2001).
Cite Us!