Differences in binding of PI 3-kinase to the src-homology domains 2 and 3 of p56 lck and p59 fyn tyrosine kinases.
Two T cell-specific src-family tyrosine kinases, p56 lck (lck) and p59 fyn (fyn), are implicated in regulating PI 3-kinase activity in response to interleukin-2 (IL-2), a cytokine that induces T cell proliferation. The src- homology domains 3 (SH3) of src-family kinases can directly interact with the PI 3-kinase regulatory subunit p85 and this may be a mechanism to regulate PI 3-kinase activity. In order to understand the mode of PI 3-kinase activation by the IL-2 receptor, we examined the association of PI 3-kinase to SH2 and SH3 domains of lck and fyn in IL-2-dependent kit 225 cells. The fyn SH3 domain bound more PI 3-kinase and its p85 subunit than the lck SH3 domain, while the lck SH2 domain bound more PI 3-kinase than the fyn SH2 domain. None of these interactions were regulated by IL-2. Low binding of PI 3-kinase to the lck SH3 domain was not observed in IL-2-independent Jurkat T cells. Thus, SH3 and SH2 domains of lck and fyn bound different amounts of PI 3-kinase, a feature that was dependent on a T cell type, but was not influenced by IL-2.
Susa
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Pharmaceutical Division, Ciba-Geigy Ltd., Basel, Switzerland.
Rohner
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Bichsel
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D018076:DNA, Complementary; D005982:Glutathione Transferase; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000302:isolation & purification / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
D018076:DNA, Complementary; D007376:Interleukin-2; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases