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

Stable Identifier
R-MMU-9680646
Type
Reaction [omitted]
Species
Mus musculus
Compartment
plasma membrane
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
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
The Pik3r1 (p85alpha) subunit of phosphatidylinositol 3-kinase (PI3K) is phosphorylated and binds Cbl and Csf1r (van der Geer and Hunter 1991, Reedijk et al. 1992, McGlade et al. 1992, van der Geer and Hunter 1993, Kanagasundaram et al. 1996, Bourette et al. 1997, Husson et al. 1997, Kanagasundaram et al. 1999, Wang et al. 1999, Ota et al. 2000, Faccio et al. 2007, Sampaio et al. 2011). Cbl also directly binds phosphorylated Csf1r (Kanagasundaram et al. 1999, Ota et al. 2000, Wilhelmsen et al. 2002, Faccio et al. 2007). Grb2:Sos1 interacts with Csf1r in response to Csf1 (Lioubin et al. 1994, Wang et al. 1999) though the interaction appears to be transient (Wang et al. 1999). Shc1 (Shc) interacts with Cbl and Csf1r (Lioubin et al. 1994 Wang et al. 1999). Cbl is constitutively bound to Grb2, Cbl is phosphorylated, and phosphorylated Cbl binds phosphorylated Shc (Wang et al. 1996, Wang et al. 1999). Plcg2 (Plc-gamma2) expressed in the myeloid lineage (Barbosa et al. 2014) binds phosphorylated tyrosine-721 of Csf1r and Plcg2 is phosphorylated in a process that requires the activity of Pi3k (Bourette et al. 1997, Bourgin-Hierle et al. 2008, Jack et al. 2009). Grap2 (Mona) binds phosphorylated tyrosine-697 of Csf1r, a site that also interacts with Grb2 (van der Geer and Hunter 1993, Bourette et al. 1998, Bourgin et al. 2000). Grab2 also binds Gab3, which is phosphorylated (Bourgin et al. 2002). 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 (Liu et al. 2001). Inppl1 (Ship2), a homolog of Inppd5 (Ship1), also binds Csf1r in response to Cdf1 (Wang et al. 2004). Gab3, a homolog of Gab2, associates with Csf1r, is phosphorylated, and interacts with Pi3k and Ptpn11 (Shp2) (Bourgin et al. 2002, Wolf et al. 2002). The Src family kinases Src, Fyn, and Yes1 (Yes) bind phosphorylated Csf1r (Kanagasundaram et al. 1999, Lee and States 2000, Rohde et al. 2004, Bourgin-Hierle et al. 2008). Stat proteins Stat1 and Stat3 bind Csf1r (Novak et al. 1995, 1996, Jack et al. 2009). Thoc5 (Fmip) binds Csf1r and is phosphorylated (Mancini et al. 2004). The order of binding and phosphorylation of interactors of Csf1r is unknown. Different subpopulations of Csf1r may be bound to different sets of interactors (Kanagasundaram et al. 1999).
Literature References
PubMed ID Title Journal Year
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Lee, AW, States, DJ

Mol. Cell. Biol. 2000
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Rohde, CM, Schrum, J, Lee, AW

J. Biol. Chem. 2004
8550554 c-Cbl is transiently tyrosine-phosphorylated, ubiquitinated, and membrane-targeted following CSF-1 stimulation of macrophages

Wang, Y, Yeung, YG, Langdon, WY, Stanley, ER

J Biol Chem 1996
11997510 Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation

Bourgin, C, Bourette, RP, Arnaud, S, Liu, Y, Rohrschneider, LR, Mouchiroud, G

Mol. Cell. Biol. 2002
11739737 Gab3, a new DOS/Gab family member, facilitates macrophage differentiation

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Mol. Cell. Biol. 2002
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Rohrschneider, LR, Bourette, RP, Lioubin, MN, Algate, PA, Myles, GM, Carlberg, K

Mol Reprod Dev 1997
9178909 CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2

Husson, H, Mograbi, B, Schmid-Antomarchi, H, Fischer, S, Rossi, B

Oncogene 1997
10648820 Association of Cbl with Fms and p85 in response to macrophage colony-stimulating factor

Ota, J, Sato, K, Kimura, F, Wakimoto, N, Nakamura, Y, Nagata, N, Suzu, S, Yamada, M, Shimamura, S, Motoyoshi, K

FEBS Lett. 2000
17972959 Src-family kinases play an essential role in differentiation signaling downstream of macrophage colony-stimulating factor receptors mediating persistent phosphorylation of phospholipase C-gamma2 and MAP kinases ERK1 and ERK2

Bourgin-Hierle, C, Gobert-Gosse, S, ThƩrier, J, Grasset, MF, Mouchiroud, G

Leukemia 2008
21610095 Phosphorylation of CSF-1R Y721 mediates its association with PI3K to regulate macrophage motility and enhancement of tumor cell invasion

Sampaio, NG, Yu, W, Cox, D, Wyckoff, J, Condeelis, J, Stanley, ER, Pixley, FJ

J. Cell. Sci. 2011
1652061 Tyrosine 706 and 807 phosphorylation site mutants in the murine colony-stimulating factor-1 receptor are unaffected in their ability to bind or phosphorylate phosphatidylinositol-3 kinase but show differential defects in their ability to induce early response gene transcription

van der Geer, P, Hunter, T

Mol. Cell. Biol. 1991
10025673 CSF-1 stimulated multiubiquitination of the CSF-1 receptor and of Cbl follows their tyrosine phosphorylation and association with other signaling proteins

Wang, Y, Yeung, YG, Stanley, ER

J. Cell. Biochem. 1999
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EMBO J. 1992
24038146 PLCĪ³2 and PKC are important to myeloid lineage commitment triggered by M-SCF and G-CSF

Barbosa, CM, Bincoletto, C, Barros, CC, Ferreira, AT, Paredes-Gamero, EJ

J. Cell. Biochem. 2014
9312046 Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-gamma2 by the M-CSF receptor is necessary for differentiation signaling

Bourette, RP, Myles, GM, Choi, JL, Rohrschneider, LR

EMBO J. 1997
17420256 M-CSF regulates the cytoskeleton via recruitment of a multimeric signaling complex to c-Fms Tyr-559/697/721

Faccio, R, Takeshita, S, Colaianni, G, Chappel, J, Zallone, A, Teitelbaum, SL, Ross, FP

J. Biol. Chem. 2007
11287610 Scaffolding protein Gab2 mediates differentiation signaling downstream of Fms receptor tyrosine kinase

Liu, Y, Jenkins, B, Shin, JL, Rohrschneider, LR

Mol. Cell. Biol. 2001
10330148 Separation and characterization of the activated pool of colony-stimulating factor 1 receptor forming distinct multimeric complexes with signalling molecules in macrophages

Kanagasundaram, V, Jaworowski, A, Byrne, R, Hamilton, JA

Mol. Cell. Biol. 1999
7579387 Colony-stimulating factor 1-induced STAT1 and STAT3 activation is accompanied by phosphorylation of Tyk2 in macrophages and Tyk2 and JAK1 in fibroblasts

Novak, U, Harpur, AG, Paradiso, L, Kanagasundaram, V, Jaworowski, A, Wilks, AF, Hamilton, JA

Blood 1995
9000134 Requirement for Y706 of the murine (or Y708 of the human) CSF-1 receptor for STAT1 activation in response to CSF-1

Novak, U, Nice, E, Hamilton, JA, Paradiso, L

Oncogene 1996
15221008 The M-CSF receptor substrate and interacting protein FMIP is governed in its subcellular localization by protein kinase C-mediated phosphorylation, and thereby potentiates M-CSF-mediated differentiation

Mancini, A, Koch, A, Whetton, AD, Tamura, T

Oncogene 2004
19587381 M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification

Jack, GD, Zhang, L, Friedman, AD

Blood 2009
1372092 SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors

McGlade, CJ, Ellis, C, Reedijk, M, Anderson, D, Mbamalu, G, Reith, AD, Panayotou, G, End, P, Bernstein, A, Kazlauskas, A

Mol. Cell. Biol. 1992
11034310 Expression of Mona (monocytic adapter) in myeloid progenitor cells results in increased and prolonged MAP kinase activation upon macrophage colony-stimulating factor stimulation

Bourgin, C, Bourette, R, Mouchiroud, G, Arnaud, S

FEBS Lett. 2000
15557176 SHIP2 is recruited to the cell membrane upon macrophage colony-stimulating factor (M-CSF) stimulation and regulates M-CSF-induced signaling

Wang, Y, Keogh, RJ, Hunter, MG, Mitchell, CA, Frey, RS, Javaid, K, Malik, AB, Schurmans, S, Tridandapani, S, Marsh, CB

J. Immunol. 2004
8262059 Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts

van der Geer, P, Hunter, T

EMBO J. 1993
8947469 Association between phosphatidylinositol-3 kinase, Cbl and other tyrosine phosphorylated proteins in colony-stimulating factor-1-stimulated macrophages

Kanagasundaram, V, Jaworowski, A, Hamilton, JA

Biochem. J. 1996
11850825 C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor's carboxy-terminus

Wilhelmsen, K, Burkhalter, S, van der Geer, P

Oncogene 2002
7520523 Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells

Lioubin, MN, Myles, GM, Carlberg, K, Bowtell, D, Rohrschneider, LR

Mol. Cell. Biol. 1994
Participants
Input
Output
Orthologous Events
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 (Homo sapiens)
Authored
May, B  (2020-03-27)
Reviewed
Stanley, ER  (2022-10-06)
Created
May, B  (2020-03-28)
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