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Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine

T E Kmiecik, D Shalloway

    Cell
    |April 10, 1987
    PubMed

    Insights

    Tyrosine phosphorylation regulates pp60c-src activity. Mutating tyrosine 527 activates the kinase, while mutating tyrosine 416 suppresses its function, revealing key regulatory mechanisms.

    Area of Science:

    • Molecular Biology
    • Cellular Signaling
    • Oncogenesis

    Background:

    • pp60c-src is a non-receptor tyrosine kinase.
    • Phosphorylation at tyrosine 527 (Tyr527) regulates pp60c-src activity in vivo.
    • Tyrosine 416 (Tyr416) is the site of in vitro autophosphorylation.

    Purpose of the Study:

    • To investigate the role of Tyr527 and Tyr416 phosphorylation in regulating pp60c-src biological activity.
    • To determine how alterations in these tyrosine residues affect kinase and transforming activities.

    Main Methods:

    • Construction and study of pp60c-src mutants with Tyr527 and Tyr416 altered to phenylalanine.
    • Assay of transforming and kinase activities of wild-type and mutant pp60c-src proteins.

    Main Results:

    • Mutation of Tyr527 to phenylalanine (Tyr527Phe) strongly activated pp60c-src transforming and kinase activities.
    • The additional introduction of a Tyr416 to phenylalanine mutation (Tyr527Phe/Tyr416Phe) suppressed these activated activities.
    • Mutation of Tyr416 to phenylalanine in normal pp60c-src eliminated its partial transforming activity.

    Conclusions:

    • Tyrosine phosphorylation at Tyr527 is a critical negative regulator of pp60c-src.
    • Phosphorylation at Tyr416 plays a role in pp60c-src function, potentially through transient or restricted phosphorylation.
    • These findings elucidate the regulatory mechanisms governing pp60c-src activity and its role in cellular processes.

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