Hierarchical scaffolding of an ERK1/2 activation pathway

Cell Communication and Signaling

Research

Ransom H Poythress¹  Qian Qian Lin¹  Kathleen G Morgan¹  Susanne Vetterkind² 

[1] Department of Health Sciences, Boston University, 02215, Boston, MA, USA;Department of Health Sciences, Boston University, 02215, Boston, MA, USA;Department of Health Sciences, Boston University, 635 Commonwealth Ave, 02215, Boston, MA, USA;

关键词: Actin;    Extracellular signal regulated kinase;    Mitogen activated kinase;    Scaffold protein;    Phorbol ester;   

DOI  :  10.1186/1478-811X-11-65

 received in 2013-03-27, accepted in 2013-08-27,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundScaffold 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.ResultsHere, 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.ConclusionsBased 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.

【 授权许可】

CC BY   
© Vetterkind et al.; licensee BioMed Central Ltd. 2013