Enhanced Phosphorylation of Src Family Kinase Substrates Containing SH2 Domain Binding Sites

摘要: Src family protein-tyrosine kinases possess several modular domains important for regulation of catalytic activity and interaction with potential substrates. Here, we explore interactions between the SH2 domain Hck, a kinase, substrates containing domain-binding sites. We have synthesized series peptide high affinity binding site, (phospho)Tyr-Glu-Glu-Ile. show that presence this sequence in results dramatic increase phosphorylation rate second tyrosine located at N terminus. Enhanced is not consequence stimulation enzymatic by C-terminal tail displacement but imparted instead 10-fold reduction K m phosphotyrosine-containing when compared control. The isolated non-receptor kinase Abl does preference pYEEI motif-containing peptide; however, restored introduced into Abl. Furthermore, enhanced dependent on distance site phosphorylatable tyrosine, minimum requirement being seven amino acids. Reversing orientation motif respect to substrate decreases down-regulated both orientations are utilized equally well activated Hck. discuss possible implications these processive vivo kinases.