+ |
CSF1R | down-regulates
phosphorylation
|
CSF1R |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-127622 |
Tyr561 |
ESYEGNSyTFIDPTQ |
Homo sapiens |
Leukemia Cell |
pmid |
sentence |
15297464 |
Csf-1-mediated wild-type (wt)-csf-1r phosphorylation was not markedly affected by sfk inhibition, indicating that lack of sfk binding is not responsible for diminished y559f phosphorylation. Unexpectedly, cells expressing y559f were hyperproliferative in response to csf-1. Hyperproliferation correlated with prolonged activation of akt, erk, and stat5 in the y559f mutant. Consistent with a defect in receptor negative regulation, c-cbl tyrosine phosphorylation and csf-1r/c-cbl co-association were almost undetectable in the y559f mutant. Furthermore, y559f underwent reduced multiubiquitination and delayed receptor internalization and degradation. In conclusion, we propose that tyr559 is a switch residue that functions in kinase regulation, signal transduction and, indirectly, receptor down-regulation. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-127626 |
Tyr969 |
PLLQPNNyQFC |
Homo sapiens |
Leukemia Cell |
pmid |
sentence |
15297464 |
Csf-1r homodimerizes and autophosphorylates on six tyrosines in the cytoplasmic portion of the receptor. Tyr807 is located in the activation loop of the kinase domain (9) and its phosphorylation is important for kinase activity (10). The remaining tyrosines serve as binding sites for proteins containing src homology 2 (sh2) binding domains. Three sites are found in the ki: grb2/mona (tyr697) (11, 12), p85 subunit of phosphatidylinositol 3-kinase (tyr721) (13), and stat1 (tyr706) (14), the c-cbl binding site is in the cooh terminus (tyr974) following ligand binding, the csf-1r is rapidly internalized and degraded. This process begins with multiubiquitination of the csf-1r mediated by c-cbl (20), an e3-type ubiquitin ligase |
|
Publications: |
2 |
Organism: |
Homo Sapiens |
+ |
CSF1R | up-regulates
phosphorylation
|
CSF1R |
0.2 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-127536 |
Tyr699 |
DPEGGVDyKNIHLEK |
Homo sapiens |
|
pmid |
sentence |
15297464 |
Csf-1r homodimerizes and autophosphorylates on six tyrosines in the cytoplasmic portion of the receptor. Tyr807 is located in the activation loop of the kinase domain (9) and its phosphorylation is important for kinase activity (10). The remaining tyrosines serve as binding sites for proteins containing src homology 2 (sh2) binding domains. Three sites are found in the ki: grb2/mona (tyr697) (11, 12), p85 subunit of phosphatidylinositol 3-kinase (tyr721) (13), and stat1 (tyr706) (14), the c-cbl binding site is in the cooh terminus (tyr974) (15, 16), and the src family kinase (sfk) binding site is in the jmd (y559) (17). These molecules further propagate the csf-1 signal through activation of ras/erk, phosphatidylinositol 3-kinase/akt, and stat proteins. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-127540 |
Tyr708 |
NIHLEKKyVRRDSGF |
Homo sapiens |
Leukemia Cell |
pmid |
sentence |
15297464 |
Csf-1r homodimerizes and autophosphorylates on six tyrosines in the cytoplasmic portion of the receptor. Tyr807 is located in the activation loop of the kinase domain (9) and its phosphorylation is important for kinase activity (10). The remaining tyrosines serve as binding sites for proteins containing src homology 2 (sh2) binding domains. Three sites are found in the ki: grb2/mona (tyr697) (11, 12), p85 subunit of phosphatidylinositol 3-kinase (tyr721) (13), and stat1 (tyr706) (14), the c-cbl binding site is in the cooh terminus (tyr974) (15, 16), and the src family kinase (sfk) binding site is in the jmd (y559) (17). These molecules further propagate the csf-1 signal through activation of ras/erk, phosphatidylinositol 3-kinase/akt, and stat proteins. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-127614 |
Tyr723 |
SSQGVDTyVEMRPVS |
Homo sapiens |
Leukemia Cell |
pmid |
sentence |
15297464 |
Csf-1r homodimerizes and autophosphorylates on six tyrosines in the cytoplasmic portion of the receptor. Tyr807 is located in the activation loop of the kinase domain (9) and its phosphorylation is important for kinase activity (10). The remaining tyrosines serve as binding sites for proteins containing src homology 2 (sh2) binding domains. Three sites are found in the ki: grb2/mona (tyr697) (11, 12), p85 subunit of phosphatidylinositol 3-kinase (tyr721) (13), and stat1 (tyr706) (14), the c-cbl binding site is in the cooh terminus (tyr974) (15, 16), and the src family kinase (sfk) binding site is in the jmd (y559) (17). These molecules further propagate the csf-1 signal through activation of ras/erk, phosphatidylinositol 3-kinase/akt, and stat proteins. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-127618 |
Tyr809 |
DIMNDSNyIVKGNAR |
Homo sapiens |
Leukemia Cell |
pmid |
sentence |
15297464 |
Csf-1r homodimerizes and autophosphorylates on six tyrosines in the cytoplasmic portion of the receptor. Tyr807 is located in the activation loop of the kinase domain (9) and its phosphorylation is important for kinase activity (10). The remaining tyrosines serve as binding sites for proteins containing src homology 2 (sh2) binding domains. Three sites are found in the ki: grb2/mona (tyr697) (11, 12), p85 subunit of phosphatidylinositol 3-kinase (tyr721) (13), and stat1 (tyr706) (14), the c-cbl binding site is in the cooh terminus (tyr974) (15, 16), and the src family kinase (sfk) binding site is in the jmd (y559) (17). These molecules further propagate the csf-1 signal through activation of ras/erk, phosphatidylinositol 3-kinase/akt, and stat proteins. |
|
Publications: |
4 |
Organism: |
Homo Sapiens |
+ |
CSF1 | up-regulates activity
binding
|
CSF1R |
0.936 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-277713 |
|
|
Homo sapiens |
Macrophage |
pmid |
sentence |
39416792 |
CSF-1, derived from fibroblasts, tumor cells, etc., is produced in membrane-bound form, secreted glycoproteins and proteoglycans. Currently, CSF-1R is considered to be the sole receptor for CSF-1. These cells regulate macrophage growth, differentiation and function by secreting CSF1. Colony-stimulating factor receptor (CSF1R), a type I single-transmembrane protein, is ubiquitously expressed in myeloid cells such as monocytes, macrophages, neuroglia, and osteoblasts. CSF1R induces receptor homodimerization by binding to either CSF-1 or IL-34, followed by activation of receptor signaling and activation of extracellular pro-cell-survival kinase cascades, including PI3K, ERK1/2, and JNK |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255568 |
|
|
Homo sapiens |
Monocyte |
pmid |
sentence |
24890514 |
The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34) |
|
Publications: |
2 |
Organism: |
Homo Sapiens |
Tissue: |
Skeletal Muscle |
+ |
FOXP1 | down-regulates quantity by repression
transcriptional regulation
|
CSF1R |
0.301 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-269048 |
|
|
Homo sapiens |
HL-60 Cell |
pmid |
sentence |
15286807 |
Overexpression of MFH/Foxp1 markedly attenuated phorbol ester-induced expression of c-fms, which encodes the M-CSF receptor and is obligatory for macrophage differentiation. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
IL34 | up-regulates activity
binding
|
CSF1R |
0.909 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-277714 |
|
|
Homo sapiens |
Macrophage |
pmid |
sentence |
39416792 |
CSF-1, derived from fibroblasts, tumor cells, etc., is produced in membrane-bound form, secreted glycoproteins and proteoglycans. Currently, CSF-1R is considered to be the sole receptor for CSF-1. These cells regulate macrophage growth, differentiation and function by secreting CSF1. Colony-stimulating factor receptor (CSF1R), a type I single-transmembrane protein, is ubiquitously expressed in myeloid cells such as monocytes, macrophages, neuroglia, and osteoblasts. CSF1R induces receptor homodimerization by binding to either CSF-1 or IL-34, followed by activation of receptor signaling and activation of extracellular pro-cell-survival kinase cascades, including PI3K, ERK1/2, and JNK |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255569 |
|
|
Homo sapiens |
Monocyte |
pmid |
sentence |
24890514 |
The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34) |
|
Publications: |
2 |
Organism: |
Homo Sapiens |
Tissue: |
Skeletal Muscle |
+ |
JNJ-28312141 free base | down-regulates activity
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-258228 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259748 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Publications: |
2 |
Organism: |
In Vitro |
+ |
1-(4-((6,7-Dimethoxyquinolin-4-yl)oxy)-2-methoxyphenyl)-3-(1-(thiazol-2-yl)ethyl)urea | down-regulates activity
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259750 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-258126 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Publications: |
2 |
Organism: |
In Vitro |
+ |
linifanib | down-regulates activity
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-258241 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Publications: |
1 |
Organism: |
In Vitro |
+ |
sunitinib | down-regulates activity
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259319 |
|
|
Homo sapiens |
|
pmid |
sentence |
17367763 |
Sunitinib (SU-11248, Sutent) inhibits at least eight receptor protein-tyrosine kinases including vascular endothelial growth factor receptors 1-3 (VEGFR1-VEGFR3), platelet-derived growth factor receptors (PDGFRalpha and PDGFRbeta), stem cell factor receptor (Kit), Flt-3, and colony-stimulating factor-1 receptor (CSF-1R). |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
CSF1R | up-regulates quantity by expression
transcriptional regulation
|
SOCS1 |
0.503 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255574 |
|
|
Homo sapiens |
|
pmid |
sentence |
24890514 |
CSF-1R also induces the expression/activation of several other regulators of multipotent progenitor proliferation/differentiation (Fig. 4A). These include […] the adaptor proteins suppressor of cytokine signaling 1 (Socs1) |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
HDLBP | down-regulates quantity by repression
transcriptional regulation
|
CSF1R |
0.35 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-266696 |
|
|
Homo sapiens |
Breast Cancer Cell |
pmid |
sentence |
33941620 |
Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, and mRNA stability and is associated with autism spectrum disorders and cancer: vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
pazopanib hydrochloride | down-regulates
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-199527 |
|
|
Homo sapiens |
|
pmid |
sentence |
Other |
|
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
CSF1R | up-regulates
|
PLCG2 |
0.376 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255570 |
|
|
Homo sapiens |
|
pmid |
sentence |
24890514 |
Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-γ2 pathway |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
5-(3-Methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine | down-regulates activity
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-258119 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-259743 |
|
|
in vitro |
|
pmid |
sentence |
22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
Publications: |
2 |
Organism: |
In Vitro |
+ |
pazopanib | down-regulates activity
chemical inhibition
|
CSF1R |
0.8 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-257740 |
|
|
Homo sapiens |
HUVEC Cell |
pmid |
sentence |
18620382 |
Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively. |
|
Publications: |
1 |
Organism: |
Homo Sapiens |
+ |
CSF1R | up-regulates
|
ERK1/2 |
0.29 |
Identifier |
Residue |
Sequence |
Organism |
Cell Line |
SIGNOR-255572 |
|
|
Homo sapiens |
|
pmid |
sentence |
24890514 |
The Erk1/2 pathway has a central role in CSF-1R-regulated myeloid differentiation. CSF-1 induces early (peaking at ∼5 min) and persistent (starting at 1 h) waves of MEK/Erk1/2 phosphorylation |
|
Publications: |
1 |
Organism: |
Homo Sapiens |