PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin

Liping Feng, Shunji Yunoue, Hiroshi Tokuo, Tatsuya Ozawa, Dongwei Zhang, Siriporn Patrakitkomjorn, Toru Ichimura, Hideyuki Saya, Norie Araki

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Neurofibromin, a neurofibromatosis type I (NF1) tumor suppressor gene product, has a domain acting as a GTPase activating protein and functions in part as a negative regulator of Ras. Loss of neurofibromin expression in NF1 patients is associated with elevated Ras activity and increased cell proliferation. Therefore, regulation of the function of neurofibromin is heavily involved in cell growth and differentiation. In the present study, we identified a novel cellular neurofibromin-associating protein, 14-3-3, which belongs to a highly conserved family of proteins that regulate intracellular signal transduction events in all eukaryotic cells. The interaction of 14-3-3 is mainly directed to the C-terminal domain (CTD) of neurofibromin, and the cAMP-dependent protein kinase (PKA)-dependent phosphorylation clustered on CTD-Ser (2576, 2578, 2580, 2813) and Thr (2556) is required for the interaction. Interestingly, the increased phosphorylation and association of 14-3-3 negatively regulate the function of neurofibromin. These findings indicate that PKA phosphorylation followed by 14-3-3 protein interaction may modulate the biochemical and biological functions of neurofibromin.

Original languageEnglish
Pages (from-to)275-282
Number of pages8
JournalFEBS Letters
Volume557
Issue number1-3
DOIs
Publication statusPublished - 2004 Jan 16
Externally publishedYes

Fingerprint

Neurofibromin 1
Phosphorylation
Neurofibromatosis 1
Protein Kinases
Tumors
Neoplasms
14-3-3 Proteins
GTPase-Activating Proteins
Signal transduction
Cell proliferation
Cell growth
Eukaryotic Cells
Cyclic AMP-Dependent Protein Kinases
Tumor Suppressor Genes
Cell Differentiation
Signal Transduction
Genes
Cell Proliferation
Association reactions

Keywords

  • 14-3-3 protein
  • cAMP-dependent protein kinase
  • GTPase activating protein
  • Neurofibromatosis type I
  • Neurofibromin
  • Tumor suppressor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Feng, L., Yunoue, S., Tokuo, H., Ozawa, T., Zhang, D., Patrakitkomjorn, S., ... Araki, N. (2004). PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin. FEBS Letters, 557(1-3), 275-282. https://doi.org/10.1016/S0014-5793(03)01507-2

PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin. / Feng, Liping; Yunoue, Shunji; Tokuo, Hiroshi; Ozawa, Tatsuya; Zhang, Dongwei; Patrakitkomjorn, Siriporn; Ichimura, Toru; Saya, Hideyuki; Araki, Norie.

In: FEBS Letters, Vol. 557, No. 1-3, 16.01.2004, p. 275-282.

Research output: Contribution to journalArticle

Feng, L, Yunoue, S, Tokuo, H, Ozawa, T, Zhang, D, Patrakitkomjorn, S, Ichimura, T, Saya, H & Araki, N 2004, 'PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin', FEBS Letters, vol. 557, no. 1-3, pp. 275-282. https://doi.org/10.1016/S0014-5793(03)01507-2
Feng, Liping ; Yunoue, Shunji ; Tokuo, Hiroshi ; Ozawa, Tatsuya ; Zhang, Dongwei ; Patrakitkomjorn, Siriporn ; Ichimura, Toru ; Saya, Hideyuki ; Araki, Norie. / PKA phosphorylation and 14-3-3 interaction regulate the function of neurofibromatosis type I tumor suppressor, neurofibromin. In: FEBS Letters. 2004 ; Vol. 557, No. 1-3. pp. 275-282.
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