Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function.

摘要: Abstract Mammalian Sprouty (Spry) proteins are now established as receptor tyrosine kinase-induced modulators of the Ras/mitogen-activated protein kinase pathway. Specifically, hSpry2 inhibits fibroblast growth factor (FGFR)-induced mitogen-activated pathway but conversely prolongs activity same following epidermal (EGF) stimulation, where activated EGF receptors retained on cell surface. In this study it is demonstrated that tyrosine-phosphorylated upon stimulation by either FGFR or and subsequently binds endogenous c-Cbl with high affinity. A conserved motif hSpry2, together phosphorylation 55, required for its enhanced interaction SH2-like domain c-Cbl. mutant (Y55F) did not exhibit an binding failed to retain Furthermore, individually mutating residues 52–59 alanine indicated a tight correlation between their affinity inhibition ERK2 in We postulate “activates” enhancing critical physiological function signal-specific context.