A 72-kilodalton fyn-related polypeptide (p72fyn-R) binds to the antigen-receptor/CD3 (TcR/CD3) complex.
Protein-tyrosine kinases play crucial roles in the activation and transformation of T lymphocytes. In this study, we have identified a variant of the fyn kinase at 70-72 kDa (termed p72fyn-R) that can preferentially associate with the TcR/CD3 complex in certain T cells. Phosphoamine acid analysis revealed that the CD3-associated p72fyn-R is labeled on both tyrosine and serine/threonine residues. TcR/CD3-associated p72fyn-R could be specifically reprecipitated using anti-fyn antisera to both the N and C terminus of p59fyn. In addition, two-dimensional phosphotryptic peptide map patterns of TcR/CD3-associated p72fyn and anti-fyn-precipitable p72 were identical. By contrast, a comparison of p72fyn-R and p62fyn showed similarities and differences. p72fyn-R possesses a peptide corresponding to the autophosphorylation site that migrates in the same position as found for p59/62fyn. However, p72fyn-R possessed at least four novel phosphorylated sites labeled on serine and threonine residues that are absent in the p62fyn pattern. Phosphatase digestion experiments indicated that p72fyn-R is more resistant to dephosphorylation than p59/62fyn. Two-dimensional phosphotryptic analysis indicated that the novel serine/threonine phosphorylation sites were responsible for the resistance to phosphatase digestion. Although the exact nature of the relationship between p72fyn-R and p59/62fyn remains undetermined, these data indicate that TcR/CD3 may utilize novel variants of src-related kinases in the generation of signals which regulate T-cell growth.
da Silva
A J
AJ
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Rudd
C E
CE
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D006224:Cricetinae; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D010449:Peptide Mapping; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D000469:Alkaline Phosphatase