Abstract

Studies during this year focused on the role of BIG1 and BIG2 on the regulation of signal transduction and regulatory pathways, focusing the potential importance of the AKAP domains, cyclic AMP-dependent as well as other protein kinases and protein phosphatases. These studies are being continued in association with my long-time collaborator, Joel Moss. Significance BIG1 and BIG2, guanine nucleotide-exchange factors (GEFs) activate Arfs by accelerating replacement of bound GDP with GTP and contain one or more AKAP sequences that scaffold multimolecular assemblies to limit cAMP signaling in space and time. Beta-catenin was among HeLa cell proteins co-immunoprecipitated with BIG1 or BIG2, and direct or indirect interactions, respectively, were demonstrated. Current studies are directed at defining other pathways regulated by BIG1 and BIG2 through their Sec7 guanine nucleotide-binding domains or through their AKAP domains. It appears that BIG1 and BIG2 are widely distributed in cells and function in variety of different pathways, depending on the proteins involved in their complexes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL000627-38
Application #
9353085
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
38
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Chen, Pei-Wen; Jian, Xiaoying; Heissler, Sarah M et al. (2016) The Arf GTPase-activating Protein, ASAP1, Binds Nonmuscle Myosin 2A to Control Remodeling of the Actomyosin Network. J Biol Chem 291:7517-26
Li, Chun-Chun; Le, Kang; Kato, Jiro et al. (2016) Enhancement of ?-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals. Proc Natl Acad Sci U S A 113:5946-51
Le, Kang; Li, Chun-Chun; Ye, Guan et al. (2013) Arf guanine nucleotide-exchange factors BIG1 and BIG2 regulate nonmuscle myosin IIA activity by anchoring myosin phosphatase complex. Proc Natl Acad Sci U S A 110:E3162-70
Lin, Sisi; Zhou, Chun; Neufeld, Edward et al. (2013) BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein modulates ATP-binding cassette transporter A-1 trafficking and function. Arterioscler Thromb Vasc Biol 33:e31-8
Shen, Xiaoyan; Li, Chun-Chun; Aponte, Angel M et al. (2012) Brefeldin A-inhibited ADP-ribosylation factor activator BIG2 regulates cell migration via integrin ?1 cycling and actin remodeling. Proc Natl Acad Sci U S A 109:14464-9
Le, Kang; Li, Ruifang; Xu, Suowen et al. (2012) PPAR? activation inhibits endothelin-1-induced cardiomyocyte hypertrophy by prevention of NFATc4 binding to GATA-4. Arch Biochem Biophys 518:71-8
Li, Chun-Chun; Kuo, Jean-Cheng; Waterman, Clare M et al. (2011) Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing. Proc Natl Acad Sci U S A 108:19228-33
Meza-Carmen, Victor; Pacheco-Rodriguez, Gustavo; Kang, Gi Soo et al. (2011) Regulation of growth factor receptor degradation by ADP-ribosylation factor domain protein (ARD) 1. Proc Natl Acad Sci U S A 108:10454-9
Puxeddu, Ermanno; Uhart, Marina; Li, Chun-Chun et al. (2009) Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity. Proc Natl Acad Sci U S A 106:6158-63
Shen, Xiaoyan; Meza-Carmen, Victor; Puxeddu, Ermanno et al. (2008) Interaction of brefeldin A-inhibited guanine nucleotide-exchange protein (BIG) 1 and kinesin motor protein KIF21A. Proc Natl Acad Sci U S A 105:18788-93

Showing the most recent 10 out of 12 publications