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Identification of conserved amino acids N-terminal of the PKCeC1bdomain crucial for PKCe-mediated induction of neurite outgrowth.

In English

Författare

  • Mia Ling
  • Ulrika Trollér
  • Ruth Zeidman
  • Helena Stensman
  • Anna Schultz
  • Christer Larsson

Summary, in English

We have shown previously that protein kinase C (PKC) epsilon can induce neurite outgrowth independently of its catalytic activity via a region encompassing its C1 domains. In this study we aimed at identifying specific amino acids in this region crucial for induction of neurite outgrowth. Deletion studies demonstrated that only 4 amino acids N-terminal and 20 residues C-terminal of the C1 domains are necessary for neurite induction. The corresponding regions from all other novel isoforms but not from PKC alpha were also neuritogenic. Further mutation studies indicated that amino acids immediately N-terminal of the C1a domain are important for plasma membrane localization and thereby for neurite induction. Addition of phorbol ester made this construct neurite-inducing. However, mutation of amino acids flanking the C1b domain reduced the neurite-inducing capacity even in the presence of phorbol esters. Sequence alignment highlighted an 8-amino acid-long sequence N-terminal of the C1b domain that is conserved in all novel PKC isoforms. Specifically, we found that mutations of either Phe-237, Val-239, or Met-241 in PKC epsilon completely abolished the neurite-inducing capacity of PKC epsilon C1 domains. Phorbol ester treatment could not restore neurite induction but led to a plasma membrane translocation. Furthermore, if 12 amino acids were included N-terminal of the C1b domain, the C1a domain was dispensable for neurite induction. In conclusion, we have identified a highly conserved sequence N-terminal of the C1b domain that is crucial for neurite induction by PKC epsilon, indicating that this motif may be critical for some morphological effects of PKC.

Publiceringsår

2005

Språk

Engelska

Sidor

17910-17919

Publikation/Tidskrift/Serie

Journal of Biological Chemistry

Volym

280

Issue

18

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Biochemistry and Molecular Biology

Ämne

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1083-351X