Both PTB domain and PH domain of IRS-1 bind inositol polyphosphates with distinct specificity

H. Takeuchi, Miho Matsuda, Takashi Kanematsu, M. Hirata

Research output: Contribution to journalArticle

Abstract

Studies in the laboratory using the recombinant pleckstrin homology (PH) domains from several proteins have confirmed our proposal that inositol phosphates/inositol lipids would be physiologically relevant ligands for the PH domain. In this study, we examined whether a phospho-tyrosine binding (PTB) domain is capable of binding specific inositol phosphates, and compared the specificity with that seen for the PH domain originated from the same protein, human insulin receptor substrate (IRS)-l. The PTB domain, the 3D structure of which is similar to that of PH domain, bound D[3H]Ins(l,4,5)P3 and the binding was displaced by Hns(l,4,5)P3 and oIns(l,3,4)P3 to the lesser extent than that by D-[ns(l,4,5)P3, indicating the specific binding. D-Ins(l,3,4,5)P4 and D-Ins(l,3,4,5,6)P5 as well as Ins?6 had the same affinity as D-Ins(l,4,5)P3. In contrast, the PH domain showed the specific preference to u-Ins(l,4,5)P3, the polar head of phosphatidylinositol 4,5-bisphosphate (PIP2). Therefore, IRS-1 is possible to be recruited for the function to the plasma membrane, in which PlPa is present, by the binding via the PH domain. On the other hand, the binding of the PTB domain to PIP2 in the plasma membrane or phosphotyrosine on the receptor molecules or adaptor molecules may be inhibited by the binding to D-Ins(l,3,4,5,6)P5 as well as InsPe which are the most abundant inositol compounds in cells.

Original languageEnglish
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - 1997

Fingerprint

Insulin Receptor Substrate Proteins
Polyphosphates
Inositol
Tyrosine
Inositol Phosphates
Cell membranes
Cell Membrane
Phosphotyrosine
Molecules
Phosphatidylinositols
platelet protein P47
Pleckstrin Homology Domains
Proteins
Ligands
Lipids
Substrates

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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Both PTB domain and PH domain of IRS-1 bind inositol polyphosphates with distinct specificity. / Takeuchi, H.; Matsuda, Miho; Kanematsu, Takashi; Hirata, M.

In: FASEB Journal, Vol. 11, No. 9, 1997.

Research output: Contribution to journalArticle

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