Adaptor signalling proteins Grb2 and Grb7 are recruited by human G6f, a novel member of the immunoglobulin superfamily encoded in the MHC.
The human G6f protein, which is encoded by a gene in the MHC, is a putative cell-surface receptor belonging to the immunoglobulin superfamily. The intracellular tail of G6f is 40 amino acids in length and contains one tyrosine residue (Y281), which is phosphorylated after treatment of cells with pervanadate. This tyrosine residue is found in a consensus-binding motif (YXN) for the Src homology 2 domains of Grb2 and Grb7 (where Grb stands for growth-factor-receptor-bound protein). Glutathione S-transferase pull-down assays showed that the interaction of G6f with both Grb2 and Grb7 is mediated through the Src homology 2 domains of these two proteins and is dependent on the phosphorylation of G6f. Immunoprecipitation experiments showed the interaction of full-length phosphorylated G6f with both full-length Grb2 and Grb7. Antibody cross-linking of G6f expressed in K562 cells resulted in a transient phosphorylation of p42/44 MAP kinase (also known as extracellular-signal-regulated protein kinase-1/2; MAP stands for mitogen-activated protein) which could be prevented by MAP kinase kinase (MEK) inhibitors. These results suggest a coupling of G6f with downstream signal transduction pathways involving Grb2 and Grb7, including the Ras-MAP kinase pathway.
De Vet
Edwin C J M
EC
MRC Rosalind Franklin Centre for Genomics Research, Hinxton, Cambridge CB10 1SB, UK.
Aguado
Begoña
B
Campbell
R Duncan
RD
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D005455:Fluorescent Antibody Technique; D051380:GRB2 Adaptor Protein; D051382:GRB7 Adaptor Protein; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D020014:K562 Cells; D008285:Major Histocompatibility Complex; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495955:GRB7 protein, human; D007136:Immunoglobulins; C477999:LY6G6F protein, human; D011506:Proteins; D051382:GRB7 Adaptor Protein; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases