IndraLab

Statements

SOS1 affects GRB2
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SOS1 binds GRB2. 10 / 600
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"Only when ligands were present did RTKs dimerize, recruit GRB2:SOS1 and generate RAS-GTP ( xref )."
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"Stoichiometry of Grb2 and Sos1 complexes at cellular concentrations."
22022247
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"The binding specificity suggests that the most likely Grb2–SOS1 binding mode is through nSH3–PVPPPVPPRRRP and cSH3–PKLPPKTYKREH interactions, which is supported by replica-exchange simulations for the Grb2–SOS1 complex models."
31970984
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"To test the extent to which the formation of Grb2-Sos1 complex with a 2:1 stoichiometry may be influenced by steric hindrance, we next measured the binding of full-length Grb2 to various single, double and triple mutant constructs of the PR domain, mutated with respect to one or more of the S1–S4 sites ( xref and xref )."
22360309
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"Based on the concentrations used for these studies, it is estimated that the affinity of SOS1 scrambled for GRB2 is greater than 50 µM. These experiments suggest that the PxxPxR motifs or sequences needed for interactions with these motifs in the context of short peptides are not required for the high-affinity binding of GRB2 to SOS1."
26079855
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"PLA assays also detected interactions between SOS1 and GRB2 in these leukemic cells, as well as other direct interactions involved in RAS activation, which also showed response to CRLF2 activation (RAS and SOS1; GRB2 and p-PTPN11)."
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"These results indicate that a direct interaction between ROS1 fusion protein with the GRB2–SOS1 complex plays an important role in the activation of MAPK pathway and the tumorigenic properties of ROS1 fusions."
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No evidence text available
11964172
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"These results suggest that small molecule targeting of SOS1 can elicit a biphasic modulation of RAS-GTP and phospho-ERK levels through negative feedback on SOS1 that regulates the interaction between SOS1 and GRB2."
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"It is possible that increased assembly of GRB2-SOS1 complex and disruption of PPP2CA-PPP2R1A complex may play a synergistic role in promoting PCa aggressiveness."
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SOS1 binds GAB1 and GRB2. 10 / 18
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"As shown in xref , it is clearly evident that the stoichiometries and energetics of binding of Sos1 and Gab1 peptides to Grb2 in Tris buffer versus Phosphate buffer are virtually indistinguishable."
20005866
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"In light of these considerations, one would expect the binding of Sos1 and Gab1 peptides to full-length Grb2 with stoichiometries of 2:1 and 1:1, respectively."
20005866
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"Given that the formation of Sos1-Grb2-Gab1 ternary signaling complex proceeds in a non-competitive manner [ xref ], the most straightforward interpretation of these salient observations is that the Sos1 peptide binds only to the nSH3 domain but not the cSH3 domain, while the Gab1 peptide binds only to the cSH3 domain in the context of full-length Grb2."
20005866
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"While we have relied here on short peptides to mimic Sos1 and Gab1, due largely to inherent difficulties associated with isolation and purification of full-length Sos1 and Gab1 proteins, it should be noted that these peptides suffice par excellence for studying the binding of Sos1 and Gab1 to Grb2 using biophysical methods."
20005866
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"Although these CD measurements are of highly qualitative nature and thus do not provide the physical basis of how the binding of Sos1 to the nSH3 domain may trigger a conformational change within Grb2 such that the nSH3 domain is only accessible to Gab1, the fact that Grb2 appears to be a highly flexible molecule by virtue of its ability to undergo discernable secondary and tertiary structural changes upon binding to Sos1 and Gab1 peptides nonetheless supports the notion that allostery is likely to play a central role in mediating communication between the nSH3 and cSH3 domains so as to allow the assembly of Sos1-Grb2-Gab1 ternary signaling complex in a non-competitive manner."
20005866
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"Grb2 binds to both the Sos1 and Gab1 peptides with a 1:1 stoichiometry."
20005866
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"FRS2 was originally discovered as a docking site for coordinated assembly of a multiprotein complex that includes GRB2, GAB1, and SOS1, and serves a critical role in the FGFR signaling pathway (Sato and Gotoh xref )."
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"The phosphatase activity of SHP2 is required for the formation of the GAB1–GRB2–SOS1 complex, which in turn promotes RAS activation xref (Fig. xref )."
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"Moreover, KIF26A did not affect Grb2 binding to Sos1 or Gab1 (M)."
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"Although efforts by others and us directed at the determination of X-ray or NMR structures of full-length Grb2 bound to Sos1 or Gab1 constructs of any sort over the past decade or so have met no success, presumably due to the transient nature of Sos1-Grb2-Gab1 complex, we have nonetheless made an attempt here to create a crude 3D structural model of how the binding of one molecule of Sos1 to the nSH3 domain may allosterically induce a conformational change within Grb2 such that the loading of a second molecule of Sos1 onto the cSH3 domain is blocked and, in so doing, allowing Gab1 access to the cSH3 domain in an exclusively non-competitive manner to generate the Sos1-Grb2-Gab1 ternary complex ( xref )."
20005866
SHC binds SOS1 and GRB2. 6 / 6
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"RTKs activates RAS in non-tumoral cells by recruiting the SHC-GRB2-SOS1 complex independently of SHP2 [72]."
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"Ligation of the BCR with anti-IgM antibodies causes an elevation of Ras-GTP levels from about 15% to 25% and coincides with the formation of complexes containing phosphorylated Shc, Grb2 and Sos1 ."
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"Both the Shc-Grb2-Sos1 complex and TGF-beta-receptor-Strap complex were included, which function in the GPCR/RTK signaling pathway and the TGF-beta-receptor signaling pathway, respectively."
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"XREF_BIBR, XREF_BIBR, XREF_BIBR In normal cells, RTKs activates Ras by recruiting the SHC, GRB2, and SOS1 complex independent of SHP2."
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"Together, these data suggest that the current model for regulation of p21ras, which proposes a stable association of Shc-grb2-Sos1 complexes at the plasma membrane, may be an oversimplification."
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"We also show that the Cbl and EGF receptor complex is predominantly associated with CrkII and is distinct to the Grb2, Shc, and Sos1 complex that associates with the EGF receptor."
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SOS1 binds CBL and GRB2. 6 / 6
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"In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL."
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"As CBL and SOS1 bind to the same region of GRB2, the overexpression of CBL inhibits complex formation between SOS1 and GRB2 underlining the fine-tuning mechanism of accessory proteins by binding other pathway modulators xref ."
34103645
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"What the actual contacts are that drive the interaction of GRB2 with either SOS1 or CBL are outside of the scope of this study."
26079855
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"Instead, as shown by our studies with the SOS1 scrambled mutant, regions outside of the consensus PxxPxR motifs drive the interaction of the complete proline rich region of SOS1 and CBL with full-length GRB2."
26079855
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"In contrast, these same PxxPxR motifs were neither necessary nor sufficient for the high affinity interaction of SOS1 or CBL with full-length GRB2 or required for the in vivo recruitment of SOS1 to the plasma membrane in activated T cells."
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"To more fully address this prediction, we utilized quantitative biophysical and imaging techniques to examine the binding of GRB2 to its physiological ligands SOS1 and CBL."
26079855
ROS1 binds SOS1 and GRB2. 3 / 3
| 3
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"To gain insight into the relationship between ROS1 fusion proteins and MAPK pathway, we performed coimmunoprecipitation analysis to look at the association of upstream MAPK activators GRB2 and SOS1 with ROS1."
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"In this study, we demonstrated that ROS1 fusion proteins can interact with the GRB2–SOS1 complex by coimmunoprecipitation studies."
32122926
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"These results indicate that a direct interaction between ROS1 fusion protein with the GRB2–SOS1 complex plays an important role in the activation of MAPK pathway and the tumorigenic properties of ROS1 fusions."
32122926
SOS1 binds EGFR and GRB2. 3 / 3
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"Upon EGF stimulation, SOS1 binds to phosphorylated EGFR through the adaptor protein GRB2, which then triggers RAS activation at the plasma membrane ."
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"Although the low-copy-number vector pBT(L) was the best in the case of EGFR-Grb2-Sos1 Y3H interaction, it may also cause reduced bait expression and lowered sensitivity for the detection of weaker protein interactions."
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"In response to stimulation with epidermal growth factor (EGF), the guanine nucleotide exchange factor human SOS1 (hSOS1) promotes the activation of Ras by forming a complex with Grb2 and the human EGF receptor (hEGFR)"
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SOS1 binds GRB2 and SH3 domains. 3 / 3
| 3
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"It is thus conceivable that the SH3 domains of Grb2 bind to Sos1 simultaneously and thereby leading to enhancement of Grb2-Sos1 interaction.In short, our data reported here provide key insights into t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Understanding the biological functions of mammalian Grb2 is complicated by the finding that the Grb2 SH3 domains potentially bind a number of protein ligands in addition to Sos1 and Sos2."
9865697
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"Subsequently, two SH3 domains of GRB2 bind the proline rich SOS1 C-terminal tail (52-55), recruiting SOS1 to the cell membrane."
30097175
SOS1 binds CBL, ATP6AP2, and GRB2. 2 / 2
| 2
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"These observations fit well with previous studies showing that SOS1 peptides bind to individual SH3 domains from GRB2 with affinities ranging from 20μM to 1mM , while the affinity for the binding of f[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26079855
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"These observations fit well with previous studies showing that SOS1 peptides bind to individual SH3 domains from GRB2 with affinities ranging from 20 µM to 1 mM [ xref – xref ], while the affinity for the binding of full-length GRB2 with full-length SOS1 or the complete PRR of SOS1 and CBL is between 300 and 400 nM ( xref ) and [ xref – xref ]."
26079855
SOS1 binds GRB2 and proline. 2 / 2
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"One LAT molecule is capable of binding up to three Grb2 molecules at a time andtwo Grb2 molecules bind one SOS1 or c-Cbl proline rich domain (XREF_FIG) 33."
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"Subsequently, two SH3 domains of GRB2 bind the proline rich SOS1 C-terminal tail (52-55), recruiting SOS1 to the cell membrane."
30097175
SHC binds SOS1, GRB2, and PTPN11. 2 / 2
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"RTKs activates RAS in non-tumoral cells by recruiting the SHC-GRB2-SOS1 complex independently of SHP2 [ xref ]."
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"RTKs activates RAS in non-tumoral cells by recruiting the SHC-GRB2-SOS1 complex independently of SHP2 [72]."
34064232
SOS1 binds CBL, LAT, and GRB2. 1 / 1
| 1
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"One such mechanism involves cooperative interactions between LAT, SOS1, c-Cbl, and GRB2 molecules, in which multiple binding sites on LAT and SOS1 or c-Cbl for the SH2 and SH3 domains of GRB2 enable oligomerization of LAT-associated signaling molecules xref ."
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SOS1 binds GRB2 and Q07889. 1 / 1
| 1
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"A large number of these PPIs are mediated by multiple SLiM classes or SLiM instances, for example, in the interaction between GRB2 (uniprot : P62993) and SOS1 (uniprot : Q07889); SOS1 has seven putative SH3 motifs and GRB2 has two SH3 domains, potentially this can equate to 14 binding interfaces for a single PPI."
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RTK binds SOS1, EGFR, and GRB2. 1 / 1
| 1
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"In xref , experimental results show that GRB2 recruits SOS1 to the membrane to form GRB2-SOS1 complex upon the activation of EGFR or other RTKs."
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SPRY binds SOS1, EGFR, GRB2, and RAF1. 1 / 1
| 1
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"Additionally, FGF1 stimulates the activation of Sprouty proteins (SPRY1-4) interacting with GRB2, SOS1, c-Raf, and epidermal growth factor receptor."
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SOS1 binds SCGB1D4 and GRB2. 1 / 1
| 1
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"There are also cases where orthologues in the invertebrates exist, but the interactions have not been observed experimentally as exemplified by the interaction of IIS and MAPK/ERK pathways via GRB2 and SOS1."
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SOS1 binds ATP6AP2 and GRB2. 1 / 1
| 1
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"These findings are in contrast to work by McDonald and coworkers, who showed that PxxPxR motifs were critical for the binding of GRB2 to the PRR or SOS1."
26079855
RRAS binds SOS1 and GRB2. 1 / 1
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"This method has found wide application in demonstrating interactions between Bcl-2 and R-Ras p23 [45] , SOS1 and GRB2 [46] , Ras and Raf [47,48] , and Raf and 14-3-3 [49] ."
10930578
GRAP2 affects GRB2, INPP5D, LCP2, SOS1, and THEMIS
| 1
SOS1 binds THEMIS, GRAP2, GRB2, INPP5D, and LCP2. 1 / 1
| 1
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"Prior to TCR engagement, GRAP2–SLP76, GRB2–SHIP1, GRB2–SOS1, and GRB2–THEMIS form stable binary complexes, leaving a large fraction of GRAP2 and GRB2 molecules in a “free” form or in complex with unknown partners ( xref )."
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FRS2 affects GAB1, GRB2, PTPN11, SH2B1, SHC1, and SOS1
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SHC1 binds SOS1, FRS2, SH2B1, GAB1, GRB2, and PTPN11. 1 / 1
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"Stimulation of different cell types with FGF-1 resulted in the formation of multiple complexes involving FRS2, GAB1, SOS1, PTPN11, SHC1, SH2B1, and GRB2 [ xref – xref ]."
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EGFR affects SPRY
| 1
SPRY binds SOS1, EGFR, GRB2, and RAF1. 1 / 1
| 1
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"Additionally, FGF1 stimulates the activation of Sprouty proteins (SPRY1-4) interacting with GRB2, SOS1, c-Raf, and epidermal growth factor receptor."
32283546
EGFR affects RTK
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RTK binds SOS1, EGFR, and GRB2. 1 / 1
| 1
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"In xref , experimental results show that GRB2 recruits SOS1 to the membrane to form GRB2-SOS1 complex upon the activation of EGFR or other RTKs."
26648121
EGFR affects RAF1
| 1
SPRY binds SOS1, EGFR, GRB2, and RAF1. 1 / 1
| 1
sparser
"Additionally, FGF1 stimulates the activation of Sprouty proteins (SPRY1-4) interacting with GRB2, SOS1, c-Raf, and epidermal growth factor receptor."
32283546
EGFR affects GRB2, RTK, and SOS1
| 1
RTK binds SOS1, EGFR, and GRB2. 1 / 1
| 1
sparser
"In xref , experimental results show that GRB2 recruits SOS1 to the membrane to form GRB2-SOS1 complex upon the activation of EGFR or other RTKs."
26648121
EGFR affects GRB2, RAF1, SOS1, and SPRY
| 1
SPRY binds SOS1, EGFR, GRB2, and RAF1. 1 / 1
| 1
sparser
"Additionally, FGF1 stimulates the activation of Sprouty proteins (SPRY1-4) interacting with GRB2, SOS1, c-Raf, and epidermal growth factor receptor."
32283546
CBL affects LAT
| 1
SOS1 binds CBL, LAT, and GRB2. 1 / 1
| 1
sparser
"One such mechanism involves cooperative interactions between LAT, SOS1, c-Cbl, and GRB2 molecules, in which multiple binding sites on LAT and SOS1 or c-Cbl for the SH2 and SH3 domains of GRB2 enable oligomerization of LAT-associated signaling molecules xref ."
30655520
ATP6AP2 affects GRB2, and SOS1
| 1
SOS1 binds ATP6AP2 and GRB2. 1 / 1
| 1
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"These findings are in contrast to work by McDonald and coworkers, who showed that PxxPxR motifs were critical for the binding of GRB2 to the PRR or SOS1."
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