Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf

Thomas M. Lanigan, Albert Liu, Yang Z. Huang, Lin Mei, Ben Margolis, Kun Liang Guan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Connector enhancer of KSR (CNK) is a multidomain protein that participates in Ras signaling in Drosophila eye development. In this report we identify the human homologue of CNK, termed CNK2A, and a truncated alternatively spliced variant, CNK2B. We characterize CNK2 phosphorylation, membrane localization, and interaction with Ras effector molecules. Our results show that MAPK signaling appears to play a role in the phosphorylation of CNK2 in vivo. CNK2 is found in both membrane and cytoplasmic fractions of the cell. In MDCK cells, full-length CNK2 is localized to the lateral plasma membrane. Consistent with previous reports, we show CNK2 interacts with Raf. CNK2 interaction was mapped to the regulatory and kinase domains of Raf, as well as to the carboxyl-terminal half of CNK2. CNK2 also interacts with the Ral signaling components, Ral GTPase, and the RalGDS family member Rlf. CNK2 interaction was mapped to the GEF domain of Rlf. The ability of CNK2 to interact with both Ras effector proteins Raf and Rlf suggests that CNK2 may integrate signals between MAPK and Ral pathways through a complex interplay of components.

Original languageEnglish (US)
Pages (from-to)2048-2060
Number of pages13
JournalFASEB Journal
Volume17
Issue number14
DOIs
StatePublished - Nov 1 2003

Fingerprint

ras Proteins
Drosophila
phosphorylation
Phosphorylation
raf Kinases
Cell Membrane
Madin Darby Canine Kidney Cells
Aptitude
GTP Phosphohydrolases
alternative splicing
guanosinetriphosphatase
Membranes
phosphotransferases (kinases)
Proteins
plasma membrane
proteins
eyes
cells
Cell membranes
Phosphotransferases

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Lanigan, T. M., Liu, A., Huang, Y. Z., Mei, L., Margolis, B., & Guan, K. L. (2003). Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. FASEB Journal, 17(14), 2048-2060. https://doi.org/10.1096/fj.02-1096com

Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. / Lanigan, Thomas M.; Liu, Albert; Huang, Yang Z.; Mei, Lin; Margolis, Ben; Guan, Kun Liang.

In: FASEB Journal, Vol. 17, No. 14, 01.11.2003, p. 2048-2060.

Research output: Contribution to journalArticle

Lanigan, TM, Liu, A, Huang, YZ, Mei, L, Margolis, B & Guan, KL 2003, 'Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf', FASEB Journal, vol. 17, no. 14, pp. 2048-2060. https://doi.org/10.1096/fj.02-1096com
Lanigan TM, Liu A, Huang YZ, Mei L, Margolis B, Guan KL. Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. FASEB Journal. 2003 Nov 1;17(14):2048-2060. https://doi.org/10.1096/fj.02-1096com
Lanigan, Thomas M. ; Liu, Albert ; Huang, Yang Z. ; Mei, Lin ; Margolis, Ben ; Guan, Kun Liang. / Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. In: FASEB Journal. 2003 ; Vol. 17, No. 14. pp. 2048-2060.
@article{cd2aeb8e861f474eb9f1447f50a53c8d,
title = "Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf",
abstract = "Connector enhancer of KSR (CNK) is a multidomain protein that participates in Ras signaling in Drosophila eye development. In this report we identify the human homologue of CNK, termed CNK2A, and a truncated alternatively spliced variant, CNK2B. We characterize CNK2 phosphorylation, membrane localization, and interaction with Ras effector molecules. Our results show that MAPK signaling appears to play a role in the phosphorylation of CNK2 in vivo. CNK2 is found in both membrane and cytoplasmic fractions of the cell. In MDCK cells, full-length CNK2 is localized to the lateral plasma membrane. Consistent with previous reports, we show CNK2 interacts with Raf. CNK2 interaction was mapped to the regulatory and kinase domains of Raf, as well as to the carboxyl-terminal half of CNK2. CNK2 also interacts with the Ral signaling components, Ral GTPase, and the RalGDS family member Rlf. CNK2 interaction was mapped to the GEF domain of Rlf. The ability of CNK2 to interact with both Ras effector proteins Raf and Rlf suggests that CNK2 may integrate signals between MAPK and Ral pathways through a complex interplay of components.",
author = "Lanigan, {Thomas M.} and Albert Liu and Huang, {Yang Z.} and Lin Mei and Ben Margolis and Guan, {Kun Liang}",
year = "2003",
month = "11",
day = "1",
doi = "10.1096/fj.02-1096com",
language = "English (US)",
volume = "17",
pages = "2048--2060",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "14",

}

TY - JOUR

T1 - Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf

AU - Lanigan, Thomas M.

AU - Liu, Albert

AU - Huang, Yang Z.

AU - Mei, Lin

AU - Margolis, Ben

AU - Guan, Kun Liang

PY - 2003/11/1

Y1 - 2003/11/1

N2 - Connector enhancer of KSR (CNK) is a multidomain protein that participates in Ras signaling in Drosophila eye development. In this report we identify the human homologue of CNK, termed CNK2A, and a truncated alternatively spliced variant, CNK2B. We characterize CNK2 phosphorylation, membrane localization, and interaction with Ras effector molecules. Our results show that MAPK signaling appears to play a role in the phosphorylation of CNK2 in vivo. CNK2 is found in both membrane and cytoplasmic fractions of the cell. In MDCK cells, full-length CNK2 is localized to the lateral plasma membrane. Consistent with previous reports, we show CNK2 interacts with Raf. CNK2 interaction was mapped to the regulatory and kinase domains of Raf, as well as to the carboxyl-terminal half of CNK2. CNK2 also interacts with the Ral signaling components, Ral GTPase, and the RalGDS family member Rlf. CNK2 interaction was mapped to the GEF domain of Rlf. The ability of CNK2 to interact with both Ras effector proteins Raf and Rlf suggests that CNK2 may integrate signals between MAPK and Ral pathways through a complex interplay of components.

AB - Connector enhancer of KSR (CNK) is a multidomain protein that participates in Ras signaling in Drosophila eye development. In this report we identify the human homologue of CNK, termed CNK2A, and a truncated alternatively spliced variant, CNK2B. We characterize CNK2 phosphorylation, membrane localization, and interaction with Ras effector molecules. Our results show that MAPK signaling appears to play a role in the phosphorylation of CNK2 in vivo. CNK2 is found in both membrane and cytoplasmic fractions of the cell. In MDCK cells, full-length CNK2 is localized to the lateral plasma membrane. Consistent with previous reports, we show CNK2 interacts with Raf. CNK2 interaction was mapped to the regulatory and kinase domains of Raf, as well as to the carboxyl-terminal half of CNK2. CNK2 also interacts with the Ral signaling components, Ral GTPase, and the RalGDS family member Rlf. CNK2 interaction was mapped to the GEF domain of Rlf. The ability of CNK2 to interact with both Ras effector proteins Raf and Rlf suggests that CNK2 may integrate signals between MAPK and Ral pathways through a complex interplay of components.

UR - http://www.scopus.com/inward/record.url?scp=0242695654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242695654&partnerID=8YFLogxK

U2 - 10.1096/fj.02-1096com

DO - 10.1096/fj.02-1096com

M3 - Article

C2 - 14597674

AN - SCOPUS:0242695654

VL - 17

SP - 2048

EP - 2060

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 14

ER -