TY - JOUR
T1 - Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions
AU - Ling, Kun
AU - Doughman, Renee L.
AU - Firestone, Ari J.
AU - Bunce, Matthew W.
AU - Anderson, Richard A.
N1 - Funding Information:
Acknowledgements HA-tagged PIPKIg mammalian expression vectors were a gift of T. F. J. Martin. We thank D. Mosher, A. Huttenlocher and P. Keely for discussions and reagents. This research was supported by the National Institutes of Health R.A.A., and by the American Heart Association for K.L., R.L.D. and M.W.B.
Funding Information:
Acknowledgements We thank L. Liu, L. Daniell and M. Caleo for technical help. We also thank T. Nagase for the gift of the human PtdInsPKIg-90 clone KIAA0589; C. Carpenter for the gift of the PtdInsPKIa and -b cDNAs; R. Hynes for the gift of mouse talin 1 cDNA; G. Cesareni and F. Felici for the phage library; and laboratory members and O. Cremona for critical discussion. This work was supported in part by grants from the NIH and from the American Diabetes Association to P.D.C. L.Pand G.C. were supported by postdoctoral fellowships from Telethon-Italia, and K.L. is a Howard Hughes Medical Institute predoctoral fellow. S.C. is a Howard Hughes Medical Institute fellow of the Life Sciences Research foundation.
PY - 2002/11/7
Y1 - 2002/11/7
N2 - The ability of cells to form cell contacts, adhere to the extracellular matrix, change morphology, and migrate is essential for development, wound healing, metastasis, cell survival and the immune response. These events depend on the binding of integrin to the extracellular matrix, and assembly of focal adhesions, which are complexes comprising scaffolding and signalling proteins organized by adhesion to the extracellular matrix1-3. Phosphatidylinositol-4, 5-bisphosphate (PtdIns(4, 5)P2) regulates interactions between these proteins, including the interaction of vinculin with actin and talin4-9. The binding of talin β-integrin is strengthened by PtdIns(4, 5)P2, suggesting that the basis of focal adhesion assembly is regulated by this lipid mediator9, 10. Here we show that the type I phosphatidylinositol phosphate kinase isoform-γ 661 (PIPKIγ661), an enzyme that makes PtdIns(4, 5)P2, is targeted to focal adhesions by an association with talin. PIPKIγ661 is tyrosine phosphorylated by focal adhesion associated kinase signalling, increasing both the activity of phosphatidylinositol phosphate kinase and its association with talin. This defines a mechanism for spatial generation of PtdIns(4, 5)P2 at focal adhesions.
AB - The ability of cells to form cell contacts, adhere to the extracellular matrix, change morphology, and migrate is essential for development, wound healing, metastasis, cell survival and the immune response. These events depend on the binding of integrin to the extracellular matrix, and assembly of focal adhesions, which are complexes comprising scaffolding and signalling proteins organized by adhesion to the extracellular matrix1-3. Phosphatidylinositol-4, 5-bisphosphate (PtdIns(4, 5)P2) regulates interactions between these proteins, including the interaction of vinculin with actin and talin4-9. The binding of talin β-integrin is strengthened by PtdIns(4, 5)P2, suggesting that the basis of focal adhesion assembly is regulated by this lipid mediator9, 10. Here we show that the type I phosphatidylinositol phosphate kinase isoform-γ 661 (PIPKIγ661), an enzyme that makes PtdIns(4, 5)P2, is targeted to focal adhesions by an association with talin. PIPKIγ661 is tyrosine phosphorylated by focal adhesion associated kinase signalling, increasing both the activity of phosphatidylinositol phosphate kinase and its association with talin. This defines a mechanism for spatial generation of PtdIns(4, 5)P2 at focal adhesions.
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U2 - 10.1038/nature01082
DO - 10.1038/nature01082
M3 - Article
C2 - 12422220
AN - SCOPUS:0037038412
SN - 0028-0836
VL - 420
SP - 89
EP - 93
JO - Nature
JF - Nature
IS - 6911
ER -