P66ShcA interacts with MAPKAP kinase 2 and regulates its activity

Abstract
Three mitogen activated protein kinase‐activated protein kinase 2 (MAPKAP kinase 2, MK2) interacting proteins were identified using a yeast two‐hybrid approach. ShcA, a signaling phospho‐protein, human polyhomeotic 2 (HPH2), a transcriptional regulator, and highly similar to smoothelin (HSTS), which is related to the cytoskeletal associated protein smoothelin, interact specifically with MK2. The interaction of MK2 with the 66 kDa isoform of ShcA, p66ShcA, and HPH2 was confirmed using co‐immunoprecipitation. MK2 is activated with p66ShcA co‐expression and p66ShcA is an in vitro substrate for MK2, further demonstrating their association and suggesting a biological role for p66Shc in MK2 activation.