A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-γ1 abolishes NGF-promoted peripherin induction but not neurite outgrowth

David M. Loeb, Robert M. Stephens, Terry Copeland, David R. Kaplan, Lloyd A. Greene

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

We analyzed the function of Trk nerve growth factor (NGF) receptors containing a point mutation (Tyr → Phe) in a major autophosphorylation site (Tyr-785). Tyr-785 is required for phospholipase C-γ1 to interact with Trk and to become tyrosine-phosphorylated in response to NGF. The altered receptors were transfected into a mutant subline of PC12 rat pheochromocytoma cells (designated PC12nnr5) that, unlike wild-type PC12 cells, lack expression of endogenous Trk and responsiveness to NGF. PC12nnr5 cells permanently transfected with Trk Y785F exhibit NGF-dependent autophosphorylation and normal NGF binding and internalization. Moreover, Trk Y785F mediates NGF-stimulated neurite outgrowth as well as a variety of additional responses including induction of immediate-early and late genes. However, in contrast to cells expressing wild-type Trk, cells expressing Trk Y785F lack NGF-promoted elevation of peripherin intermediate filament mRNA and protein. These observations indicate that phospholipase C-γ1 activation or other signaling pathways dependent on Tyr-785 autophosphorylation are selectively required for regulation of peripherin expression by NGF, but not for many other functional NGF responses. This supports the presence of multiple and separable signaling pathways in the NGF mechanism of action.

Original languageEnglish (US)
Pages (from-to)8901-8910
Number of pages10
JournalJournal of Biological Chemistry
Volume269
Issue number12
StatePublished - Mar 25 1994
Externally publishedYes

Fingerprint

Peripherins
Nerve Growth Factor Receptor
Type C Phospholipases
Nerve Growth Factor
Point Mutation
Cells
Nerve Growth Factor Receptors
Intermediate Filament Proteins
Neuronal Outgrowth
Immediate-Early Genes
PC12 Cells
Pheochromocytoma
Tyrosine
Rats
Genes
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-γ1 abolishes NGF-promoted peripherin induction but not neurite outgrowth. / Loeb, David M.; Stephens, Robert M.; Copeland, Terry; Kaplan, David R.; Greene, Lloyd A.

In: Journal of Biological Chemistry, Vol. 269, No. 12, 25.03.1994, p. 8901-8910.

Research output: Contribution to journalArticle

@article{4310a54cbad64a8180a7251c8de392b6,
title = "A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-γ1 abolishes NGF-promoted peripherin induction but not neurite outgrowth",
abstract = "We analyzed the function of Trk nerve growth factor (NGF) receptors containing a point mutation (Tyr → Phe) in a major autophosphorylation site (Tyr-785). Tyr-785 is required for phospholipase C-γ1 to interact with Trk and to become tyrosine-phosphorylated in response to NGF. The altered receptors were transfected into a mutant subline of PC12 rat pheochromocytoma cells (designated PC12nnr5) that, unlike wild-type PC12 cells, lack expression of endogenous Trk and responsiveness to NGF. PC12nnr5 cells permanently transfected with Trk Y785F exhibit NGF-dependent autophosphorylation and normal NGF binding and internalization. Moreover, Trk Y785F mediates NGF-stimulated neurite outgrowth as well as a variety of additional responses including induction of immediate-early and late genes. However, in contrast to cells expressing wild-type Trk, cells expressing Trk Y785F lack NGF-promoted elevation of peripherin intermediate filament mRNA and protein. These observations indicate that phospholipase C-γ1 activation or other signaling pathways dependent on Tyr-785 autophosphorylation are selectively required for regulation of peripherin expression by NGF, but not for many other functional NGF responses. This supports the presence of multiple and separable signaling pathways in the NGF mechanism of action.",
author = "Loeb, {David M.} and Stephens, {Robert M.} and Terry Copeland and Kaplan, {David R.} and Greene, {Lloyd A.}",
year = "1994",
month = "3",
day = "25",
language = "English (US)",
volume = "269",
pages = "8901--8910",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - A Trk nerve growth factor (NGF) receptor point mutation affecting interaction with phospholipase C-γ1 abolishes NGF-promoted peripherin induction but not neurite outgrowth

AU - Loeb, David M.

AU - Stephens, Robert M.

AU - Copeland, Terry

AU - Kaplan, David R.

AU - Greene, Lloyd A.

PY - 1994/3/25

Y1 - 1994/3/25

N2 - We analyzed the function of Trk nerve growth factor (NGF) receptors containing a point mutation (Tyr → Phe) in a major autophosphorylation site (Tyr-785). Tyr-785 is required for phospholipase C-γ1 to interact with Trk and to become tyrosine-phosphorylated in response to NGF. The altered receptors were transfected into a mutant subline of PC12 rat pheochromocytoma cells (designated PC12nnr5) that, unlike wild-type PC12 cells, lack expression of endogenous Trk and responsiveness to NGF. PC12nnr5 cells permanently transfected with Trk Y785F exhibit NGF-dependent autophosphorylation and normal NGF binding and internalization. Moreover, Trk Y785F mediates NGF-stimulated neurite outgrowth as well as a variety of additional responses including induction of immediate-early and late genes. However, in contrast to cells expressing wild-type Trk, cells expressing Trk Y785F lack NGF-promoted elevation of peripherin intermediate filament mRNA and protein. These observations indicate that phospholipase C-γ1 activation or other signaling pathways dependent on Tyr-785 autophosphorylation are selectively required for regulation of peripherin expression by NGF, but not for many other functional NGF responses. This supports the presence of multiple and separable signaling pathways in the NGF mechanism of action.

AB - We analyzed the function of Trk nerve growth factor (NGF) receptors containing a point mutation (Tyr → Phe) in a major autophosphorylation site (Tyr-785). Tyr-785 is required for phospholipase C-γ1 to interact with Trk and to become tyrosine-phosphorylated in response to NGF. The altered receptors were transfected into a mutant subline of PC12 rat pheochromocytoma cells (designated PC12nnr5) that, unlike wild-type PC12 cells, lack expression of endogenous Trk and responsiveness to NGF. PC12nnr5 cells permanently transfected with Trk Y785F exhibit NGF-dependent autophosphorylation and normal NGF binding and internalization. Moreover, Trk Y785F mediates NGF-stimulated neurite outgrowth as well as a variety of additional responses including induction of immediate-early and late genes. However, in contrast to cells expressing wild-type Trk, cells expressing Trk Y785F lack NGF-promoted elevation of peripherin intermediate filament mRNA and protein. These observations indicate that phospholipase C-γ1 activation or other signaling pathways dependent on Tyr-785 autophosphorylation are selectively required for regulation of peripherin expression by NGF, but not for many other functional NGF responses. This supports the presence of multiple and separable signaling pathways in the NGF mechanism of action.

UR - http://www.scopus.com/inward/record.url?scp=0028245830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028245830&partnerID=8YFLogxK

M3 - Article

C2 - 7510697

AN - SCOPUS:0028245830

VL - 269

SP - 8901

EP - 8910

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -