Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling.
Shc protein is tyrosine phosphorylated upon B cell receptor (BCR) activation and after its phosphorylation interacts with the adaptor protein Grb2. In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Several protein-tyrosine kinases (PTKs) participate in BCR signaling. However, it is not clear which PTK is involved in the phosphorylation of Shc, resulting in coupling to the Ras pathway. Tyrosine phosphorylation of Shc and its association with Grb2 were profoundly reduced in both Lyn- and Syk-deficient B cells upon BCR stimulation. Furthermore, kinase activity of these PTKs was required for phosphorylation of Shc. Shc interacted with Syk in B cells. This interaction and the requirement of Syk kinase activity for phosphorylation of Shc were also demonstrated by cotransfection in COS cells. Because Lyn is required for activation of Syk upon receptor stimulation, our results suggest that the Lyn-activated Syk phosphorylates Shc during BCR signaling.
Nagai
K
K
Department of Biochemistry, Fukui Medical School, Japan.
Takata
M
M
Yamamura
H
H
Kurosaki
T
T
D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000502:physiology*; D051380:GRB2 Adaptor Protein; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D000072377:Syk Kinase; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases
D048868:Adaptor Proteins, Signal Transducing; D004792:Enzyme Precursors; D051380:GRB2 Adaptor Protein; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051076:Proto-Oncogene Proteins c-fyn; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases