CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration

Myriam A. Attar, Joseph C. Salem, Heather S. Pursel, Lorraine C. Santy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Epithelial cells are largely immotile under normal circumstances, but become motile during development, repair of tissue damage and during cancer metastasis. Numerous growth factors act to initiate epithelial cell movements. Hepatocyte growth factor (HGF) induces many epithelial cell lines to begin crawling. A number of small GTPases act downstream of HGF to alter cell shape and promote movement. Arf6 is one of these GTPases that can alter the cortical actin cytoskeleton and promote epithelial movement. Activation of Arf6 in MDCK cells by its guanine nucleotide exchange factor cytohesin 2/ARNO produces a scattering response strikingly reminiscent of the action of HGF. We have previously shown that IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin-induced scattering. We report here that IPCEF1 is actually the C-terminal half of CNK3. CNKs are scaffolds involved in signal transduction downstream of Ras. We have found that both MDCK and CaCo-2 cells express a fused CNK3/IPCEF1 protein. Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment.

Original languageEnglish (US)
Pages (from-to)228-237
Number of pages10
JournalExperimental Cell Research
Volume318
Issue number3
DOIs
StatePublished - Feb 1 2012

Fingerprint

Hepatocyte Growth Factor
Epithelial Cells
Proteins
Guanine Nucleotide Exchange Factors
Madin Darby Canine Kidney Cells
Caco-2 Cells
Monomeric GTP-Binding Proteins
Cell Shape
GTP Phosphohydrolases
Actin Cytoskeleton
Cell Movement
Signal Transduction
Intercellular Signaling Peptides and Proteins
Neoplasm Metastasis
Cell Line
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Attar, Myriam A. ; Salem, Joseph C. ; Pursel, Heather S. ; Santy, Lorraine C. / CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration. In: Experimental Cell Research. 2012 ; Vol. 318, No. 3. pp. 228-237.
@article{6dc98abdd1cd43348b66c1c2b75ffc0c,
title = "CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration",
abstract = "Epithelial cells are largely immotile under normal circumstances, but become motile during development, repair of tissue damage and during cancer metastasis. Numerous growth factors act to initiate epithelial cell movements. Hepatocyte growth factor (HGF) induces many epithelial cell lines to begin crawling. A number of small GTPases act downstream of HGF to alter cell shape and promote movement. Arf6 is one of these GTPases that can alter the cortical actin cytoskeleton and promote epithelial movement. Activation of Arf6 in MDCK cells by its guanine nucleotide exchange factor cytohesin 2/ARNO produces a scattering response strikingly reminiscent of the action of HGF. We have previously shown that IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin-induced scattering. We report here that IPCEF1 is actually the C-terminal half of CNK3. CNKs are scaffolds involved in signal transduction downstream of Ras. We have found that both MDCK and CaCo-2 cells express a fused CNK3/IPCEF1 protein. Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment.",
author = "Attar, {Myriam A.} and Salem, {Joseph C.} and Pursel, {Heather S.} and Santy, {Lorraine C.}",
year = "2012",
month = "2",
day = "1",
doi = "10.1016/j.yexcr.2011.10.018",
language = "English (US)",
volume = "318",
pages = "228--237",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "3",

}

CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration. / Attar, Myriam A.; Salem, Joseph C.; Pursel, Heather S.; Santy, Lorraine C.

In: Experimental Cell Research, Vol. 318, No. 3, 01.02.2012, p. 228-237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration

AU - Attar, Myriam A.

AU - Salem, Joseph C.

AU - Pursel, Heather S.

AU - Santy, Lorraine C.

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Epithelial cells are largely immotile under normal circumstances, but become motile during development, repair of tissue damage and during cancer metastasis. Numerous growth factors act to initiate epithelial cell movements. Hepatocyte growth factor (HGF) induces many epithelial cell lines to begin crawling. A number of small GTPases act downstream of HGF to alter cell shape and promote movement. Arf6 is one of these GTPases that can alter the cortical actin cytoskeleton and promote epithelial movement. Activation of Arf6 in MDCK cells by its guanine nucleotide exchange factor cytohesin 2/ARNO produces a scattering response strikingly reminiscent of the action of HGF. We have previously shown that IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin-induced scattering. We report here that IPCEF1 is actually the C-terminal half of CNK3. CNKs are scaffolds involved in signal transduction downstream of Ras. We have found that both MDCK and CaCo-2 cells express a fused CNK3/IPCEF1 protein. Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment.

AB - Epithelial cells are largely immotile under normal circumstances, but become motile during development, repair of tissue damage and during cancer metastasis. Numerous growth factors act to initiate epithelial cell movements. Hepatocyte growth factor (HGF) induces many epithelial cell lines to begin crawling. A number of small GTPases act downstream of HGF to alter cell shape and promote movement. Arf6 is one of these GTPases that can alter the cortical actin cytoskeleton and promote epithelial movement. Activation of Arf6 in MDCK cells by its guanine nucleotide exchange factor cytohesin 2/ARNO produces a scattering response strikingly reminiscent of the action of HGF. We have previously shown that IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin-induced scattering. We report here that IPCEF1 is actually the C-terminal half of CNK3. CNKs are scaffolds involved in signal transduction downstream of Ras. We have found that both MDCK and CaCo-2 cells express a fused CNK3/IPCEF1 protein. Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment.

UR - http://www.scopus.com/inward/record.url?scp=84855823851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855823851&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2011.10.018

DO - 10.1016/j.yexcr.2011.10.018

M3 - Article

C2 - 22085542

AN - SCOPUS:84855823851

VL - 318

SP - 228

EP - 237

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 3

ER -