HIP1 and HIP1r Stabilize Receptor Tyrosine Kinases and Bind 3-Phosphoinositides Via Epsin N-terminal Homology Domains

Teresa S. Hyun, Dinesh S. Rao, Djenann Saint-Dic, L. Evan Michael, Priti D. Kumar, Sarah V. Bradley, Ikuko F. Mizukami, Katherine I. Oravecz-Wilson, Theodora S. Ross

Research output: Contribution to journalArticle

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Abstract

Huntingtin-interacting protein 1-related (HIP1r) is the only known mammalian relative of huntingtin-interacting protein 1 (HIP1), a protein that transforms fibroblasts via undefined mechanisms. Here we demonstrate that both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains. In contrast to other ENTH domain-containing proteins, lipid binding is preferential to the 3-phosphate-containing inositol lipids, phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,5-bisphosphate. Furthermore, the HIP1r ENTH 'domain, like that of HIP1, is necessary for lipid binding, and expression of an ENTH domain-deletion mutant, HIP1r/ΔE, induces apoptosis. Consistent with the ability of HIP1r and HIP1 to affect cell survival, full-length HIP1 and HIP1r stabilize pools of growth factor receptors by prolonging their half-life following ligand-induced endocytosis. Although HIP1r and HIP1 display only a partially overlapping pattern of protein interactions, these data suggest that both proteins share a functional homology by binding 3-phosphorylated inositol lipids and stabilizing receptor tyrosine kinases in a fashion that may contribute to their ability to alter cell growth and survival.

Original languageEnglish (US)
Pages (from-to)14294-14306
Number of pages13
JournalJournal of Biological Chemistry
Volume279
Issue number14
DOIs
StatePublished - Apr 2 2004

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Receptor Protein-Tyrosine Kinases
Phosphatidylinositols
Proteins
Lipids
Inositol
epsin
Huntingtin Protein
Cell Survival
Growth Factor Receptors
Endocytosis
Protein Binding
Half-Life
Cell growth
Fibroblasts

ASJC Scopus subject areas

  • Biochemistry

Cite this

HIP1 and HIP1r Stabilize Receptor Tyrosine Kinases and Bind 3-Phosphoinositides Via Epsin N-terminal Homology Domains. / Hyun, Teresa S.; Rao, Dinesh S.; Saint-Dic, Djenann; Michael, L. Evan; Kumar, Priti D.; Bradley, Sarah V.; Mizukami, Ikuko F.; Oravecz-Wilson, Katherine I.; Ross, Theodora S.

In: Journal of Biological Chemistry, Vol. 279, No. 14, 02.04.2004, p. 14294-14306.

Research output: Contribution to journalArticle

Hyun, Teresa S. ; Rao, Dinesh S. ; Saint-Dic, Djenann ; Michael, L. Evan ; Kumar, Priti D. ; Bradley, Sarah V. ; Mizukami, Ikuko F. ; Oravecz-Wilson, Katherine I. ; Ross, Theodora S. / HIP1 and HIP1r Stabilize Receptor Tyrosine Kinases and Bind 3-Phosphoinositides Via Epsin N-terminal Homology Domains. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 14. pp. 14294-14306.
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