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 (Mason et al. 2004). SRC kinase also phosphorylates numerous tyrosine residues in the C terminal region of SPRY2 including Y227, in response to FGF but not EGF stimulation. 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.