Magicin associates with the Src-family kinases and is phosphorylated upon CD3 stimulation

Biochem Biophys Res Commun. 2006 Sep 29;348(3):826-31. doi: 10.1016/j.bbrc.2006.07.126. Epub 2006 Jul 31.

Abstract

We recently identified a novel actin cytoskeleton-associated protein magicin, for merlin and Grb2 interacting cytoskeletal protein. To unravel the cellular functions of magicin, we used a yeast two-hybrid system and identified Fyn tyrosine kinase as a specific binding partner for magicin. Fyn phosphorylates magicin in vitro. In addition to Fyn, Src and Lck also interact with magicin. Upon stimulation with anti-CD3 antibody, magicin is phosphorylated in the T lymphocyte leukemia Jurkat cell line. Magicin phosphorylation is not observed in an Lck-deficient line, J.CaM1.6, indicating that Lck is the major Src family kinase for phosphorylating magicin in Jurkat cells. Employing site-directed mutagenesis along with in vitro kinase assays, we found that Y64 of magicin is phosphorylated by Lck creating a SH2-Grb2 binding motif. Magicin has also been identified as a Mediator subunit (MED28) in the nucleus involved in transcriptional regulation, therefore we propose that magicin may serve as a multi-faceted adaptor/scaffold to relay cellular signaling to the cytoskeleton and from the cytoskeleton to the nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CD3 Complex / physiology*
  • Cell Line
  • Cell Nucleus / physiology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Jurkat Cells
  • Mediator Complex
  • Mice
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Proto-Oncogene Proteins c-fyn / metabolism
  • Signal Transduction / physiology
  • src-Family Kinases / physiology*

Substances

  • CD3 Complex
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • MED28 protein, human
  • Mediator Complex
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases