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 βI (PKCβI). Here, we show that when ENH1 is co-expressed, PKCβI is translocated from the cytoplasm to the plasma membrane in the absence of any other stimulation. Moreover expression of ENH1 markedly increases PKCβI activity in the absence of PKC activators. A similar activation of PKCβI 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 PKCβI activation. Finally, interaction with ENH1 also increases the activity of PKCα and PKCγ, whereas it reduces PKCζ 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.
Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan. maturana@vos.nagaokaut.ac.jp
Andrés D
AD
Maturana
Noritaka
N
Nakagawa
Nobuo
N
Yoshimoto
Kenji
K
Tatematsu
Masahiko
M
Hoshijima
Katsuyuki
K
Tanizawa
Shun'ichi
S
Kuroda
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D060588:LIM Domain Proteins; D054731:PDZ Domains; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016335:Zinc Fingers
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C512485:PDLIM5 protein, human; D018808:Transcription Factor AP-1; C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon