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Hierarchical scaffolding of an ERK1/2 activation pathway.

Authors: Vetterkind, S  Poythress, RH  Lin, QQ  Morgan, KG 
Citation: Vetterkind S, etal., Cell Commun Signal. 2013 Aug 29;11:65. doi: 10.1186/1478-811X-11-65.
Pubmed: (View Article at PubMed) PMID:23987506
DOI: Full-text: DOI:10.1186/1478-811X-11-65

BACKGROUND: Scaffold proteins modulate cellular signaling by facilitating assembly of specific signaling pathways. However, there is at present little information if and how scaffold proteins functionally interact with each other. RESULTS: Here, we show that two scaffold proteins, caveolin-1 and IQGAP1, are required for phosphorylation of the actin associated pool of extracellular signal regulated kinase 1 and 2 (ERK1/2) in response to protein kinase C activation. We show by immunofluorescence and proximity ligation assays, that IQGAP1 tethers ERK1/2 to actin filaments. Moreover, siRNA experiments demonstrate that IQGAP1 is required for activation of actin-bound ERK1/2. Caveolin-1 is also necessary for phosphorylation of actin-bound ERK1/2 in response to protein kinase C, but is dispensible for ERK1/2 association with actin. Simultaneous knock down of caveolin-1 and IQGAP1 decreases total phorbol ester-induced ERK1/2 phosphorylation to the same degree as single knock down of either caveolin-1 or IQGAP1, indicating that caveolin-1 and IQGAP1 operate in the same ERK activation pathway. We further show that caveolin-1 knock down, but not IQGAP1 knock down, reduces C-Raf phosphorylation in response to phorbol ester stimulation. CONCLUSIONS: Based on our data, we suggest that caveolin-1 and IQGAP1 assemble distinct signaling modules, which are then linked in a hierarchical arrangement to generate a functional ERK1/2 activation pathway.

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CRRD Object Information
CRRD ID: 11049533
Created: 2016-04-07
Species: All species
Last Modified: 2016-04-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.