Abstract
FOCAL adhesion kinase1,2 (pp125FAK) is a member of a growing family of structurally distinct protein tyrosine kinases that includes the recently identified FakB3 and PYK2/CAKβ/ RAFTK4,6. Activation of pp125FAK has been functionally linked to the formation of focal adhesions, integrin-mediated sites of contact between the cell and the extracellular matrix7,8. The carboxy-terminal domain of pp125FAK is also expressed as a separate protein called pp41/43FRNK(where FRNK represents pp125FAK-related non-kinase)9. Here we show that pp41/43FRNK acts as an inhibitor of pp125FAK by transiently blocking the formation of focal adhesions on fibronectin and constitutively reducing tyrosine phosphorylation of both pp125FAK and of two focal adhesion proteins, tensin and paxillin. These inhibitory effects of pp41/43FRNK are reversed by co-expression of pp!25FAK, suggesting that pp125FAK and pp41/43FRNK compete for a common binding protein(s) whose association with pp125FAK is necessary for signalling by pp125FAK. We propose that pp41/43FRNK functions as an endogenous regulator of pp125FAK, thus providing an unusual means to regulate both tyrosine kinase activity and cellular adhesion to the extracellular matrix.
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Richardson, A., Parsons, J. A mechanism for regulation of the adhesion-associated protein tyrosine kinase pp125FAK. Nature 380, 538–540 (1996). https://doi.org/10.1038/380538a0
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DOI: https://doi.org/10.1038/380538a0
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