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Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf 1
Author(s) -
Lanigan Thomas M.,
Liu Albert,
Huang Yang Z.,
Mei Lin,
Margolis Ben,
Guan Kun-Liang
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1096com
Subject(s) - effector , microbiology and biotechnology , phosphorylation , cytoplasm , enhancer , gtpase , mapk/erk pathway , biology , kinase , small gtpase , sh3 domain , signal transduction , genetics , gene , gene expression , proto oncogene tyrosine protein kinase src
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 Ral‐GDS 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.—Lanigan T. M., Liu A., Huang Y. Z., Mei L., Margolis B., Guan K.‐L. Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf. FASEB J. 17, 2048–2060 (2003)