LIM domains regulate protein kinase C activity: A novel molecular function

Enigma homolog protein 1 (ENH1) acts as a scaffold that selectively associates protein kinases and transcription factors with cytoskeletal elements. ENH1 comprises an N-terminal PDZ domain and three C-terminal LIM domains. Through the LIM domains ENH1 interacts with the N-terminal region of protein kinase C beta I (PKC beta I). Here, we show that when ENH1 is co-expressed, PKC beta I is translocated from the cytoplasm to the plasma membrane in the absence of any other stimulation. Moreover expression of ENH1 markedly increases PKC beta I activity in the absence of PKC activators. A similar activation of PKC beta I was observed with co-expression of Cypher1 or Enigma, but not other LIM proteins. The region including the three LIM domains of ENH1 (residues 415-591) appears to be sufficient for this PKC beta 1 activation. Finally, interaction with ENH1 also increases the activity of PKC alpha and PKC gamma, whereas it reduces PKC zeta activity. These findings provide strong evidence that ENH1 activates conventional PKCs by directly binding through its LIM domains. Thus. LIM domains have a novel molecular function: the regulation of PKC activities in a PKC isoform-specific manner. (C) 2011 Elsevier Inc. All rights reserved.