A novel calmodulin-beta-PIX interaction and its implication in receptor tyrosine kinase regulation

作者：Singh Vinay K; Munro Kim; Jia Zongchao^*

来源：Cellular Signalling, 2012, 24(9): 1790-1796.

DOI：10.1016/j.cellsig.2012.05.005

• Calmodulin
• beta-PIX
• Calcium binding
• Cell signaling
• Protein-protein interaction
• Receptor tyrosine kinase

Calmodulin (CaM), a ubiquitous calcium-binding protein, regulates numerous cellular processes, primarily in response to calcium flux. We have identified and characterized a novel interaction between CaM and beta-p21-activated kinase interacting exchange factor (beta-PIX), a putative guanine exchange factor implicated in cell signaling, using affinity pull-down assays, co-immunoprecipitation, co-localization and circular dichroism studies. Fluorescence-based titration and isothermal titration calorimetry experiments revealed a Ca2+-dependent binding mechanism (K-D %26lt;= 10 mu M). Further, we show that CaM participates in a multi-protein complex involving beta-PIX and E3 ubiquitin ligase c-Cbl (casitas B-cell lymphoma), which may play a critical role in receptor tyrosine kinase regulation and downstream signaling.

• 出版日期2012-9