Extracellular Signal-Regulated Kinase 1c (ERK1c), a novel 42-kilodalton ERK, demonstrates unique modes of regulation, localization, and function

Daniel M. Aebersold, Yoav D. Shaul, Yuval Yung, Nirit Yarom, Zhong Yao, Tamar Hanoch, Rony Seger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Extracellular signal-regulated kinases (ERKs) are signaling molecules that regulate many cellular processes. We have previously identified an alternatively spliced 46-kDa form of ERK1 that is expressed in rats and mice and named ERK1b. Here we report that the same splicing event in humans and monkeys causes, due to sequence differences in the inserted introns, the production of an ERK isoform that migrates together with the 42-kDa ERK2. Because of the differences of this isoform from ERK1b, we named it ERK1c. We found that its expression levels are about 10% of ERK1. ERK1c seems to be expressed in a wide variety of tissues and cells. Its activation by MEKs and inactivation by phosphatases are slower than those of ERK1, which is probably the reason for its differential regulation in response to extracellular stimuli. Unlike ERK1, ERK1c undergoes mono-ubiquitination, which is increased with elevated cell density concomitantly with accumulation of ERK1c in the Golgi apparatus. Elevated cell density also causes enhanced Golgi fragmentation, which is facilitated by overexpression of native ERK1c and is prevented by dominant-negative ERK1c, indicating that ERK1c mediates cell density-induced Golgi fragmentation. The differential regulation of ERK1c extends the signaling specificity of MEKs after stimulation by various extracellular stimuli.

Original languageAmerican English
Pages (from-to)10000-10015
Number of pages16
JournalMolecular and Cellular Biology
Volume24
Issue number22
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Dive into the research topics of 'Extracellular Signal-Regulated Kinase 1c (ERK1c), a novel 42-kilodalton ERK, demonstrates unique modes of regulation, localization, and function'. Together they form a unique fingerprint.

Cite this