Regulation of Syk by phosphorylation on serine in the linker insert.
The Syk protein-tyrosine kinase is phosphorylated on multiple tyrosines after the aggregation of the B cell antigen receptor. However, metabolic labeling experiments indicate that Syk is inducibly phosphorylated to an even greater extent on serine after receptor ligation. A combination of phosphopeptide mapping and mass spectrometric analyses indicates that serine 291 is a major site of phosphorylation. Serine 291 lies within a 23-amino acid insert located within the linker B region that distinguishes Syk from SykB and Zap-70. The phosphorylation of serine-291 by protein kinase C enhances the ability of Syk to couple the antigen receptor to the activation of the transcription factors NFAT and Elk-1. Protein interaction studies indicate a role for the phosphorylated linker insert in promoting an interaction between Syk and the chaperone protein, prohibitin.
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA.
Leela L
LL
Paris
Jianjie
J
Hu
Jacob
J
Galan
Su Sien
SS
Ong
Victoria A
VA
Martin
Haiyan
H
Ma
W Andy
WA
Tao
Marietta L
ML
Harrison
Robert L
RL
Geahlen
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010449:Peptide Mapping / Q000379:methods; D010766:Phosphorylation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D000072377:Syk Kinase; D020298:U937 Cells; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
C494112:ELK1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050778:NFATC Transcription Factors; D011947:Receptors, Antigen, B-Cell; D050807:ets-Domain Protein Elk-1; D012694:Serine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human