PIK3R1:PIK3CA,B,D (PI3K), PLCG2 (PLCgamma2), SHC1 (SHC), PTPN11 (SHP2), GRB2:GAB2, GRB2:GAB3, GRAP2 (MONA), CBL:GRB2, INPP5D (SHIP1), INPPL1 (SHIP2) bind PolyUb,p-8Y-CSF1R and are activated

Stable Identifier
R-HSA-9680348
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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PIK3R1:PIK3CA,B,D (PI3K), PLCG2 (PLCgamma2), SHC1 (SHC), PTPN11 (SHP2), GRB2:GAB2, GRB2:GAB3, GRAP2 (MONA), CBL:GRB2, INPP5D (SHIP1), INPPL1 (SHIP2) bind PolyUb,p-8Y-CSF1R and are activated
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The PIK3R1 (p85alpha) subunit of phosphatidylinositol 3-kinase (PI3K) is phosphorylated and binds CBL and CSF1R (inferred from mouse homologs). CBL also directly binds phosphorylated CSF1R (inferred from mouse homologs). GRB2:SOS1 transiently interacts with CSF1R (inferred from mouse homologs) and PI3K (Saleem et al. 1995) in response to CSF1. SHC1 (SHC) interacts with CBL and CSF1R (inferred from mouse homologs). CBL is constitutively bound to GRB2, CBL is phosphorylated, and phosphorylated CBL binds phosphorylated SHC (inferred from mouse homologs). PLCG2 (PLC-gamma2), expressed in the myeloid lineage, binds phosphorylated tyrosine-723 of CSF1R and PLCG2 is phosphorylated in a process that requires the activity of PI3K (inferred from mouse homologs). GRAP2 (MONA) binds phosphorylated tyrosine-699 of CSF1R. GRB2 also interacts with CSF1R (Kharbanda et al. 1995) via phosphotyrosine-699 ( inferred from mouse homologs). GRAP2 binds GAB3, which is then phosphorylated (inferred from mouse homologs). In response to CSF1, the scaffolding protein GAB2 associates with INPP5D (SHIP1) and other proteins involved in CSF1 signaling and GAB2 is phosphorylated directly or indirectly by CSF1R (inferred from mouse homologs). INPPD5D also interacts with the kinase LYN (Baran et al. 2003). INPPL1 (SHIP2), a homolog of INPPD5, binds CSF1R in response to CSF1 (inferred from mouse homologs). GAB3, a homolog of GAB2, associates with CSF1R, is phosphorylated, and interacts with PI3K and PTPN11 (SHP2) (inferred from mouse homologs). The SRC family kinases SRC, FYN, and YES1 (YES) bind phosphorylated CSF1R (Courtneidge et al. 1993, Li et al. 1997, also inferred from mouse homologs). STAT proteins STAT1 and STAT3 bind CSF1R and are phosphorylated (inferred from mouse homologs). STAT5 also appears to be phosphorylated in response to CSF1 (Knowlton et al. 2010). THOC5 (FMIP) binds CSF1R and is phosphorylated (inferred from mouse homologs). The order of binding and phosphorylation of the interactors of CSF1R is unknown. Different subpopulations of CSF1R may be bound to different sets of interactors (inferred from mouse homologs).
Literature References
PubMed ID Title Journal Year
12882960 The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity

Humphries, RK, Tridandapani, S, Helgason, CD, Baran, CP, Marsh, CB, Krystal, G

J. Biol. Chem. 2003
7597091 Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin

Emoto, Y, Saleem, A, Yuan, Z, Kharbanda, S, Kufe, D, Prasad, KV

Proc. Natl. Acad. Sci. U.S.A. 1995
9225065 Bryostatin 1 (bryo1)-induced monocytic differentiation in THP-1 human leukemia cells is associated with enhanced c-fyn tyrosine kinase and M-CSF receptors

Li, Y, Varterasian, ML, Chen, B, Mohammad, RM, al-Katib, A

Leuk. Res. 1997
7681396 Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor

Waterfield, MD, Pilat, D, Twamley, GM, Courtneidge, SA, Roussel, MF, Dhand, R

EMBO J. 1993
7737969 Monocyte colony-stimulating factor stimulates binding of phosphatidylinositol 3-kinase to Grb2.Sos complexes in human monocytes

Saleem, A, Kharbanda, S, Kufe, D, Yuan, ZM

J. Biol. Chem. 1995
21049007 Profiling Y561-dependent and -independent substrates of CSF-1R in epithelial cells

Gygi, SP, Gu, TL, Knowlton, ML, Wrobel, CN, Brugge, JS, Polakiewicz, R, Ballif, BA, Selfors, LM

PLoS ONE 2010
Participants
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Output
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as an event of
Inferred From
Pik3r11:Pik3ca,b,d (Pi3k), Plcg2 (PLCgamma2), Grb2:Sos1, Shc1 (Shc), Ptpn11 (Shp2), Grb2:Gab2, Grb2:Gab3, Grap2 (MONA), Cbl:Grb2, Inpp5d (SHIP1), Inppl1 (SHIP2) bind p-8Y-Csf1r and are activated (Mus musculus)
Authored
May, B  (2020-03-14)
Reviewed
Stanley, ER  (2022-10-06)
Created
May, B  (2020-03-27)
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