Fyn phosphorylates human MAP-2c on tyrosine 67

Zamora-Leon, SP; Bresnick, A; Backer, JM; Shafit-Zagardo, B

Abstract

The Src homology 3 (SH3) domain of Fyn binds to a conserved PXXP motif on microtubule-associated protein-2. Co-transfections into COS7 cells and in vitro kinase assays performed with Fyn and wild-type, or mutant MAP-2c, determined that Fyn phosphorylated MAP-2c on tyrosine 67. The phosphorylation generated a consensus sequence for the binding of the SH2 domain of Grb2 (pYSN). Pull-down assays with SH2-Grb2 from human fetal brain homogenates, and co-immunoprecipitation of Grb2 and MAP-2 confirmed the interaction in vivo, and demonstrated that MAP-2c is tyrosine-phosphorylated in human fetal brain. Filter overlay assays confirmed that the SH2 domain of Grb2 binds to human MAP-2c following incubation with active Fyn. Enzyme-linked immunosorbent assays confirmed the interaction between the SH2 domain of Grb2 and a tyrosine-phosphorylated MAP-2 peptide spanning the pY(67)SN motif. Thus, MAP-2c can directly recruit multiple signaling proteins important for central nervous system development.

Más información

Título según WOS: ID WOS:000226341700030 Not found in local WOS DB
Título de la Revista: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 280
Número: 3
Editorial: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Fecha de publicación: 2005
Página de inicio: 1962
Página final: 1970
DOI:

10.1074/jbc.M411380200

Notas: ISI