Premium
ERK1/2 Signaling through Scaffold Protein Shoc2 Complexing with H, K, and M‐Ras: A Structure‐Function Analysis
Author(s) -
Norcross Rebecca,
Galperin Emilia
Publication year - 2017
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/fasebj.31.1_supplement.930.3
Subject(s) - scaffold protein , gene isoform , biology , signal transduction , microbiology and biotechnology , function (biology) , motility , effector , biochemistry , gene
The extracellularly‐regulated kinase ‐1 and ‐2 (ERK1/2) signaling pathway utilizes a network of proteins and signaling events to control many downstream effectors for cell proliferation, apoptosis, differentiation, and motility. The broad scope of ERK1/2's branched signaling capacity requires integrated fine‐tuning for specific signaling control. To this end, the pathway utilizes scaffolding proteins – essential regulatory proteins to facilitate the activities of enzymes in the pathway. Shoc2, the critical scaffolding protein within the ERK1/2 pathway, serves as a platform to create a temporal and spatial microenvironment for effective protein complex formation and signal transduction. The scaffold facilitates the interaction between Ras and Raf‐1 thereby accelerating ERK1/2 signaling. Our earlier studies show that Shoc2 also transduces ERK1/2 motility signals. All canonical Ras isoforms (H, K, and M) have been reported to interact with Shoc2. We previously determined that M‐Ras recognizes Shoc2 sequences within the Shoc2's N‐terminal domain (amino residues 1‐82). Yet, the mechanisms responsible for the Shoc2 interaction with other Ras isoforms have not been defined. In this study, we are analyzing the structure‐function relationship of Shoc2 with different Ras isoforms and identifying the underlying mechanisms of these interactions. Biochemical and biophysical methods including immunoprecipitations, fluorescence microscopy and in vitro complex reconstitution are utilized. Moreover, any variation in downstream effects of Shoc2 differential binding to Ras isoforms will be determined. This study will also identify the specificity of Shoc2‐mediated ERK1/2 signals achieved via binding to the Ras isoforms. By deciphering the intricate details of protein interactions within the Shoc2's signaling module, we will expand our knowledge of how specificity of ERk1/2 signaling is achieved and controlled. Support or Funding Information Funding sources: National Institute of General Medical Sciences, American Cancer Society