Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction

Jennifer L. Rudolph; Geng Xian Shi; Eda Erdogan; Alan P. Fields; Douglas A. Andres

doi:10.1016/j.bbamcr.2007.09.008

Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction

Jennifer L. Rudolph, Geng Xian Shi, Eda Erdogan, Alan P. Fields, Douglas A. Andres

Cancer Biology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Rit is a novel member of the Ras superfamily of small GTP-binding proteins that regulates signaling pathways controlling cellular fate determination. Constitutively activated mutants of Rit induce terminal differentiation of pheochromocytoma (PC6) cells resulting in a sympathetic neuron-like phenotype characterized by the development of highly-branched neurites. Rit signaling has been found to activate several downstream pathways including MEK/ERK, p38 MAPK, Ral-specific guanine nucleotide exchange factors (GEFs), and Rit associates with the Par6 cell polarity machinery. In this study, a series of Rit effector loop mutants was generated to test the importance of these cellular targets to Rit-mediated neuronal differentiation. We find that Rit-mediated neuritogenesis is dependent upon MEK/ERK MAP kinase signaling but independent of RalGEF activation. In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling.

Original language	English (US)
Pages (from-to)	1793-1800
Number of pages	8
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1773
Issue number	12
DOIs	https://doi.org/10.1016/j.bbamcr.2007.09.008
State	Published - Dec 2007

Keywords

ERK MAP kinase
GTPase
Neuronal differentiation
PC12 cell
Par6
Ras
Rit

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbamcr.2007.09.008

Cite this

@article{826e8bbec8b34e0b88ae570395a6ddf8,

title = "Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction",

abstract = "Rit is a novel member of the Ras superfamily of small GTP-binding proteins that regulates signaling pathways controlling cellular fate determination. Constitutively activated mutants of Rit induce terminal differentiation of pheochromocytoma (PC6) cells resulting in a sympathetic neuron-like phenotype characterized by the development of highly-branched neurites. Rit signaling has been found to activate several downstream pathways including MEK/ERK, p38 MAPK, Ral-specific guanine nucleotide exchange factors (GEFs), and Rit associates with the Par6 cell polarity machinery. In this study, a series of Rit effector loop mutants was generated to test the importance of these cellular targets to Rit-mediated neuronal differentiation. We find that Rit-mediated neuritogenesis is dependent upon MEK/ERK MAP kinase signaling but independent of RalGEF activation. In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling.",

keywords = "ERK MAP kinase, GTPase, Neuronal differentiation, PC12 cell, Par6, Ras, Rit",

author = "Rudolph, {Jennifer L.} and Shi, {Geng Xian} and Eda Erdogan and Fields, {Alan P.} and Andres, {Douglas A.}",

note = "Funding Information: This work was supported by Public Health Service grant NS045103 (to D.A.A) from the National Institute of Neurological Disorders and Stroke, by Grant P20RR20171 from the COBRE program of the National Center for Research Resources, a Predoctoral Fellowship from the Ohio Valley Affiliate of the American Heart Association (to J.L.R.), the National Institutes of Health (CA81436 to A.P.F), The James and Esther King Biomedical Research Program and the American Lung Association/LUNGevity Foundation (to A.P.F.). We thank Dr. Ian Macara for the generous gift of reagents.",

year = "2007",

month = dec,

doi = "10.1016/j.bbamcr.2007.09.008",

language = "English (US)",

volume = "1773",

pages = "1793--1800",

journal = "Biochimica et Biophysica Acta - Molecular Cell Research",

issn = "0167-4889",

publisher = "Elsevier",

number = "12",

}

TY - JOUR

T1 - Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction

AU - Rudolph, Jennifer L.

AU - Shi, Geng Xian

AU - Erdogan, Eda

AU - Fields, Alan P.

AU - Andres, Douglas A.

N1 - Funding Information: This work was supported by Public Health Service grant NS045103 (to D.A.A) from the National Institute of Neurological Disorders and Stroke, by Grant P20RR20171 from the COBRE program of the National Center for Research Resources, a Predoctoral Fellowship from the Ohio Valley Affiliate of the American Heart Association (to J.L.R.), the National Institutes of Health (CA81436 to A.P.F), The James and Esther King Biomedical Research Program and the American Lung Association/LUNGevity Foundation (to A.P.F.). We thank Dr. Ian Macara for the generous gift of reagents.

PY - 2007/12

Y1 - 2007/12

N2 - Rit is a novel member of the Ras superfamily of small GTP-binding proteins that regulates signaling pathways controlling cellular fate determination. Constitutively activated mutants of Rit induce terminal differentiation of pheochromocytoma (PC6) cells resulting in a sympathetic neuron-like phenotype characterized by the development of highly-branched neurites. Rit signaling has been found to activate several downstream pathways including MEK/ERK, p38 MAPK, Ral-specific guanine nucleotide exchange factors (GEFs), and Rit associates with the Par6 cell polarity machinery. In this study, a series of Rit effector loop mutants was generated to test the importance of these cellular targets to Rit-mediated neuronal differentiation. We find that Rit-mediated neuritogenesis is dependent upon MEK/ERK MAP kinase signaling but independent of RalGEF activation. In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling.

AB - Rit is a novel member of the Ras superfamily of small GTP-binding proteins that regulates signaling pathways controlling cellular fate determination. Constitutively activated mutants of Rit induce terminal differentiation of pheochromocytoma (PC6) cells resulting in a sympathetic neuron-like phenotype characterized by the development of highly-branched neurites. Rit signaling has been found to activate several downstream pathways including MEK/ERK, p38 MAPK, Ral-specific guanine nucleotide exchange factors (GEFs), and Rit associates with the Par6 cell polarity machinery. In this study, a series of Rit effector loop mutants was generated to test the importance of these cellular targets to Rit-mediated neuronal differentiation. We find that Rit-mediated neuritogenesis is dependent upon MEK/ERK MAP kinase signaling but independent of RalGEF activation. In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling.

KW - ERK MAP kinase

KW - GTPase

KW - Neuronal differentiation

KW - PC12 cell

KW - Par6

KW - Ras

KW - Rit

UR - http://www.scopus.com/inward/record.url?scp=36548998835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36548998835&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2007.09.008

DO - 10.1016/j.bbamcr.2007.09.008

M3 - Article

C2 - 17976838

AN - SCOPUS:36548998835

SN - 0167-4889

VL - 1773

SP - 1793

EP - 1800

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 12

ER -

Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this