Tyrosine phosphorylation of the orphan receptor ESDN/DCBLD2 serves as a scaffold for the signaling adaptor CrkL

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• 作者：Tyler M. Aten ; Mir ; a M. Redmond ; Sheila O. Weaver ; Collin C. Love ; Ryan M. Joy ; Aliya S. Lapp ; Osvaldo D. Rivera ; Karen L. Hinkle ; Bryan A. Ballif
• 关键词：ESDN ; endothelial and smooth muscle cell-derived neuropilin-like protein ; DCBLD2 ; discoidin CUB and LCCL domain containing 2 ; CUB ; complement C1r/C1s Uegf Bmp1 ; CrkL ; CrkCT10 regulator of kinase Crk-Like ; SFK ; Src family tyrosine kinase ; Cas ; Crk-associat
• 刊名：FEBS Letters
• 出版年：2013
• 出版时间：2 August, 2013
• 年：2013
• 卷：587
• 期：15
• 页码：2313-2318
• 全文大小：1333 K

文摘

A quantitative proteomics screen to identify substrates of the Src family of tyrosine kinases (SFKs) whose phosphorylation promotes CrkL-SH2 binding identified the known Crk-associated substrate (Cas) of Src as well as the orphan receptor endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN). Mutagenesis analysis of ESDN¡¯s seven intracellular tyrosines in YxxP motifs found several contribute to the binding of ESDN to the SH2 domains of both CrkCT10 regulator of kinase Crk-Like (CrkL) and a representative SFK Fyn. Quantitative mass spectrometry showed that at least three of these (Y565, Y621 and Y750), as well as non-YxxP Y715, are reversibly phosphorylated. SFK activity was shown to be sufficient, but not required for the interaction between ESDN and the CrkL-SH2 domain. Finally, antibody-mediated ESDN clustering induces ESDN tyrosine phosphorylation and CrkL-SH2 binding.