Protein sprouty homologue 2 (SPRY2) belongs to the sprouty family, whose members are inhibitors of the Ras-ERK pathway downstream of various receptor tyrosine kinases []. SPRY2 functions as a negative regulator of receptor tyrosine kinase/ERK signaling pathway and is involved in many biological processes, including cell growth, differentiation, migration, and embryonic lung branching morphogenesis [, ]. It inhibits FGF-RAS-ERK signaling by binding to growth factor receptor bound protein 2 (GRB2) during fibroblast growth factor receptor (FGFR) activation, disrupting the GRB2-SOS (son of sevenless) complex that transduces signals from FGFR to RAS [, ].
This SPRY domain (SPRY2) is the second of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, The SPRY2 domain has been shown to bind to the dihydropryidine receptor (DHPR) II-III loop and the ASI region of RyR1 [, ].
