Reactome | SRC phosphorylates SPRY2 on Y55 and Y227

SRC phosphorylates SPRY2 on Y55 and Y227

Stable Identifier

R-HSA-1295609

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Signaling by Receptor Tyrosine Kinases (Homo sapiens)
  - Signaling by FGFR (Homo sapiens)
    - Signaling by FGFR1 (Homo sapiens)
      - Negative regulation of FGFR1 signaling (Homo sapiens)
        
        Spry regulation of FGF signaling (Homo sapiens)
        
        SRC phosphorylates SPRY2 on Y55 and Y227 (Homo sapiens)
    - Signaling by FGFR2 (Homo sapiens)
      - Negative regulation of FGFR2 signaling (Homo sapiens)
        
        Spry regulation of FGF signaling (Homo sapiens)
        
        SRC phosphorylates SPRY2 on Y55 and Y227 (Homo sapiens)
    - Signaling by FGFR3 (Homo sapiens)
      - Negative regulation of FGFR3 signaling (Homo sapiens)
        
        Spry regulation of FGF signaling (Homo sapiens)
        
        SRC phosphorylates SPRY2 on Y55 and Y227 (Homo sapiens)
    - Signaling by FGFR4 (Homo sapiens)
      - Negative regulation of FGFR4 signaling (Homo sapiens)
        
        Spry regulation of FGF signaling (Homo sapiens)
        
        SRC phosphorylates SPRY2 on Y55 and Y227 (Homo sapiens)

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SRC phosphorylates SPRY2 on Y55 and Y227

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Sprouty 2 protein is phosphorylated on tyrosine residue 55. The ability of SRC kinase to catalyze this reaction has been demonstrated with purified proteins in vitro (Li et al. 2004) and in cultured cells with studies of the effects of SRC-family pharmacological inhibitors and of dominant-negative mutant SRC proteins (Rubin et al, 2005). SRC kinase also phosphorylates numerous tyrosine residues in the C terminal region of SPRY2 including Y227, in response to FGF but not EGF stimulation (Rubin et al, 2005; Fong et al, 2003). SRC-mediated phosphorylation of SPRY2 at Y55 is negatively regulated by MNK1-dependent serine phosphorylation of SPRY2. MNK1-mediated SPRY2 phosphorylation stabilizes SPRY2 by antagonizing tyrosine phosphorylation and CBL binding, thus limiting ubiquitin-mediated degradation (Da Silva et al, 2006).

Literature References

PubMed ID	Title	Journal	Year
15637081	Phosphorylation of carboxyl-terminal tyrosines modulates the specificity of Sprouty-2 inhibition of different signaling pathways Yarden, Y, Ron, D, Vaisman, N, Zwang, Y, Rubin, C	J Biol Chem	2005
15564375	FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity Brunton, VG, Burgar, HR, Heath, JK, Li, X, Wheldon, LM	J Cell Sci	2004
12815057	Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function Yusoff, P, Fong, CW, Wong, ES, Lim, J, Leong, HF, Guy, GR	J Biol Chem	2003
16479008	Regulation of sprouty stability by Mnk1-dependent phosphorylation Xu, L, Miller, WT, DaSilva, J, Kim, HJ, Bar-Sagi, D	Mol Cell Biol	2006