Identification of Grb4/Nckβ, a Src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck

Lara E. Braverman, Lawrence Quilliam

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Adapter proteins made up of Src homology (SH) domains mediate multiple cellular signaling events initiated by receptor protein tyrosine kinases. Here we report that Grb4 is an adapter protein closely related to but distinct from Nck that is made up of three SH3 domains and one SH2 domain. Northern analysis indicated that both genes are expressed in multiple tissues. Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2, and they synergized with v-Abl and Sos to induce gene expression via the transcription factor Elk-1. Although neither protein was transforming on its own, both Nck and Grb4 cooperated with v-Abl to transform NIH 3T3 cells and influenced the morphology and anchorage-dependent growth of wild type Ras-transformed cells. Nck and Grb4 therefore appear to be functionally redundant.

Original languageEnglish
Pages (from-to)5542-5549
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number9
DOIs
StatePublished - Feb 26 1999

Fingerprint

src Homology Domains
Receptor Protein-Tyrosine Kinases
ets-Domain Protein Elk-1
NIH 3T3 Cells
Proteins
Cell signaling
Carrier Proteins
Gene expression
Gene Expression
Genes
Tissue
Growth

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{2c0a10a7e7a44addae9d369e6fd13d7f,
title = "Identification of Grb4/Nckβ, a Src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck",
abstract = "Adapter proteins made up of Src homology (SH) domains mediate multiple cellular signaling events initiated by receptor protein tyrosine kinases. Here we report that Grb4 is an adapter protein closely related to but distinct from Nck that is made up of three SH3 domains and one SH2 domain. Northern analysis indicated that both genes are expressed in multiple tissues. Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2, and they synergized with v-Abl and Sos to induce gene expression via the transcription factor Elk-1. Although neither protein was transforming on its own, both Nck and Grb4 cooperated with v-Abl to transform NIH 3T3 cells and influenced the morphology and anchorage-dependent growth of wild type Ras-transformed cells. Nck and Grb4 therefore appear to be functionally redundant.",
author = "Braverman, {Lara E.} and Lawrence Quilliam",
year = "1999",
month = "2",
day = "26",
doi = "10.1074/jbc.274.9.5542",
language = "English",
volume = "274",
pages = "5542--5549",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "9",

}

TY - JOUR

T1 - Identification of Grb4/Nckβ, a Src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck

AU - Braverman, Lara E.

AU - Quilliam, Lawrence

PY - 1999/2/26

Y1 - 1999/2/26

N2 - Adapter proteins made up of Src homology (SH) domains mediate multiple cellular signaling events initiated by receptor protein tyrosine kinases. Here we report that Grb4 is an adapter protein closely related to but distinct from Nck that is made up of three SH3 domains and one SH2 domain. Northern analysis indicated that both genes are expressed in multiple tissues. Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2, and they synergized with v-Abl and Sos to induce gene expression via the transcription factor Elk-1. Although neither protein was transforming on its own, both Nck and Grb4 cooperated with v-Abl to transform NIH 3T3 cells and influenced the morphology and anchorage-dependent growth of wild type Ras-transformed cells. Nck and Grb4 therefore appear to be functionally redundant.

AB - Adapter proteins made up of Src homology (SH) domains mediate multiple cellular signaling events initiated by receptor protein tyrosine kinases. Here we report that Grb4 is an adapter protein closely related to but distinct from Nck that is made up of three SH3 domains and one SH2 domain. Northern analysis indicated that both genes are expressed in multiple tissues. Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2, and they synergized with v-Abl and Sos to induce gene expression via the transcription factor Elk-1. Although neither protein was transforming on its own, both Nck and Grb4 cooperated with v-Abl to transform NIH 3T3 cells and influenced the morphology and anchorage-dependent growth of wild type Ras-transformed cells. Nck and Grb4 therefore appear to be functionally redundant.

UR - http://www.scopus.com/inward/record.url?scp=0033604899&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033604899&partnerID=8YFLogxK

U2 - 10.1074/jbc.274.9.5542

DO - 10.1074/jbc.274.9.5542

M3 - Article

C2 - 10026169

AN - SCOPUS:0033604899

VL - 274

SP - 5542

EP - 5549

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 9

ER -