The neuronal adaptor protein Fe65 is phosphorylated by mitogen-activated protein kinase (ERK1/2).
Fe65 is a neuronal adaptor protein that binds a number of ligands and which functions in both gene transcription/nuclear signalling and in the regulation of cell migration and motility. These different functions within the nucleus and at the cell surface are mediated via Fe65's different binding partners. An Fe65/APP/TIP60 complex is transcriptionally active within the nucleus and an Fe65/APP/Mena complex probably regulates actin dynamics in lamellipodia. The mechanisms that regulate these different Fe65 functions are unclear. Here, we demonstrate that Fe65 is a phosphoprotein and, using mass spectrometry sequencing, identify for the first time in vivo phosphorylation sites in Fe65. We also show that Fe65 is a substrate for phosphorylation by the mitogen-activated protein kinases ERK1/2. Our results provide a mechanism by which Fe65 function may be modulated to fulfil its various roles.
Standen
Claire L
CL
Department of Neuroscience, The Institute of Psychiatry, Kings College, London, UK.
Perkinton
Michael S
MS
Byers
Helen L
HL
Kesavapany
Sashi
S
Lau
Kwok-Fai
KF
Ward
Malcolm
M
McLoughlin
Declan
D
Miller
Christopher C J
CC
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation
C466684:APBB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases