IQGAP1 binds ERK2 and modulates its activity
- PMID: 14970219
- DOI: 10.1074/jbc.M308405200
IQGAP1 binds ERK2 and modulates its activity
Abstract
IQGAP1 binds several proteins including actin, calmodulin, E-cadherin, beta-catenin, Cdc42, Rac1, and CLIP-170. The interaction with these targets enables IQGAP1 to participate in many cellular functions varying from regulation of the cytoskeleton to gene transcription. Here we show that extracellular signal-regulated kinase (ERK) 2 binds to IQGAP1. In vitro analysis with purified proteins demonstrated a direct interaction between ERK2 and IQGAP1. Moreover, binding occurred in cells as endogenous ERK2 co-immunoprecipitated with IQGAP1 from human breast epithelial cell lysates. The association between ERK2 and IQGAP1 was independent of epidermal growth factor. The in vivo interaction has functional significance. Manipulation of intracellular IQGAP1 levels significantly reduced growth factor-stimulated ERK1 and ERK2 activity. Similarly, stimulation of ERK1 and ERK2 activity by insulin-like growth factor I was reduced when IQGAP1 levels were changed. In contrast, overexpression of an IQGAP1 construct lacking the ERK2 binding region did not interfere with activation of ERK1 and ERK2 by epidermal growth factor. Our data disclose a previously unidentified communication between IQGAP1 and the ERK pathway and imply that IQGAP1 modulates the Ras/mitogen-activated protein kinase signaling cascade.
Similar articles
-
The activation of Rac1 by M3 muscarinic acetylcholine receptors involves the translocation of Rac1 and IQGAP1 to cell junctions and changes in the composition of protein complexes containing Rac1, IQGAP1, and actin.J Biol Chem. 2002 Sep 6;277(36):33081-91. doi: 10.1074/jbc.M202664200. Epub 2002 Jun 17. J Biol Chem. 2002. PMID: 12070151
-
IQGAP1 is a scaffold for mitogen-activated protein kinase signaling.Mol Cell Biol. 2005 Sep;25(18):7940-52. doi: 10.1128/MCB.25.18.7940-7952.2005. Mol Cell Biol. 2005. PMID: 16135787 Free PMC article.
-
Hyaluronan-CD44 interaction with IQGAP1 promotes Cdc42 and ERK signaling, leading to actin binding, Elk-1/estrogen receptor transcriptional activation, and ovarian cancer progression.J Biol Chem. 2005 Mar 25;280(12):11961-72. doi: 10.1074/jbc.M411985200. Epub 2005 Jan 17. J Biol Chem. 2005. PMID: 15655247
-
IQGAP1 in cellular signaling: bridging the GAP.Trends Cell Biol. 2006 May;16(5):242-9. doi: 10.1016/j.tcb.2006.03.002. Epub 2006 Apr 3. Trends Cell Biol. 2006. PMID: 16595175 Review.
-
IQGAPs in cancer: a family of scaffold proteins underlying tumorigenesis.FEBS Lett. 2009 Jun 18;583(12):1817-24. doi: 10.1016/j.febslet.2009.05.007. Epub 2009 May 9. FEBS Lett. 2009. PMID: 19433088 Free PMC article. Review.
Cited by
-
Navigating the ERK1/2 MAPK Cascade.Biomolecules. 2023 Oct 20;13(10):1555. doi: 10.3390/biom13101555. Biomolecules. 2023. PMID: 37892237 Free PMC article. Review.
-
Hax1 regulate focal adhesion dynamics through IQGAP1.Cell Commun Signal. 2023 Jul 24;21(1):182. doi: 10.1186/s12964-023-01189-y. Cell Commun Signal. 2023. PMID: 37488602 Free PMC article.
-
Haldol Targets IQGAP1 Pathway and Promotes Novel Partner Interactions in Glioblastoma Cell Lines.MicroPubl Biol. 2023 May 8;2023:10.17912/micropub.biology.000822. doi: 10.17912/micropub.biology.000822. eCollection 2023. MicroPubl Biol. 2023. PMID: 37228393 Free PMC article.
-
The WW domain of IQGAP1 binds directly to the p110α catalytic subunit of PI 3-kinase.Biochem J. 2023 May 5:BCJ20220493. doi: 10.1042/BCJ20220493. Online ahead of print. Biochem J. 2023. PMID: 37145016
-
The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.J Cell Biol. 2023 Jun 5;222(6):e202205062. doi: 10.1083/jcb.202205062. Epub 2023 Apr 18. J Cell Biol. 2023. PMID: 37071417 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
