title: Magicin associates with the Src-family kinases and is phosphorylated upon CD3 stimulation.
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.
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Ming-Fen
authors.initials: MF
authors.lastname: Lee
authors.forename: Roberta L
authors.initials: RL
authors.lastname: Beauchamp
authors.forename: Kim S
authors.initials: KS
authors.lastname: Beyer
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Vijaya
authors.initials: V
authors.lastname: Ramesh
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D056892:Mediator Complex; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology*
chemical_list: D017252:CD3 Complex; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C496877:MED28 protein, human; D056892:Mediator Complex; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases