Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Immunology
IF: 1.404 5-Year IF: 3.347 SJR: 0.706 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Volumes:
Volume 40, 2020 Volume 39, 2019 Volume 38, 2018 Volume 37, 2017 Volume 36, 2016 Volume 35, 2015 Volume 34, 2014 Volume 33, 2013 Volume 32, 2012 Volume 31, 2011 Volume 30, 2010 Volume 29, 2009 Volume 28, 2008 Volume 27, 2007 Volume 26, 2006 Volume 25, 2005 Volume 24, 2004 Volume 23, 2003 Volume 22, 2002 Volume 21, 2001 Volume 20, 2000 Volume 19, 1999 Volume 18, 1998 Volume 17, 1997 Volume 16, 1996 Volume 15, 1995 Volume 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i3.70
pages 299-304

The Intertwining of Structure and Function: Proposed Helix-Swapping of the SH2 Domain of Grb7, A Regulatory Protein Implicated in Cancer Progression and Inflammation

Sally Pias
New Mexico State University
Tabitha A. Peterson
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico
Dennis L. Johnson
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico
Barbara A. Lyons
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico

ABSTRACT

Grb7 is a multidomain intracellular signaling protein that links activated tyrosine kinases with downstream signaling targets. Best known for its regulatory role in cell migration and tumor metastasis, Grb7 also regulates inflammation by coupling NF-kappaB-inducing kinase with erbB/EGFR family receptors. The "adaptor" role of Grb7 in these processes depends upon binding to membrane-associated tyrosine kinases through its C-terminal SH2 domain. The Grb7-SH2 domain shares structural and functional similarity with the SH2 domain of Grb2, a constituent of the MAP kinase pathway. Both domains show unusual affinity for cyclic (beta-turn) ligands. The Grb2-SH2 domain also shows distinctive self-association behavior, forming intertwined ("swapped") dimers. While Grb7 and its SH2 domain are each known to dimerize, the mechanisms and functional significance of this self-association are incompletely understood. Additional residues in the Grb7-SH2 domain effectively lengthen its "EF loop" and render the domain a good candidate for swapped dimerization, through exchange of a C-terminal helix. We propose the existence of a swapped dimeric form of the Grb7-SH2 domain and offer a structural model derived through novel application of nuclear magnetic resonance-derived restraints


Articles with similar content:

Targeting the ATF-1/CREB Transcription Factors by Single Chain Fv Fragment in Human Melanoma: Potential Modality for Cancer Therapy
Critical Reviews™ in Immunology, Vol.21, 2001, issue 1-3
Menashe Bar-Eli, Didier Jean
Clinical Significance of the Inhibition of YY1 Activity and Expression by Therapeutic Anti-Cancer Antibodies
Forum on Immunopathological Diseases and Therapeutics, Vol.1, 2010, issue 1-2
Sara Huerta-Yepez, Demetrios A. Spandidos, Norio Uematsu, Mario I. Vega, Loredana Militello, Ali R. Jazirehi, Stavroula Baritaki, Benjamin Bonavida
Raf Kinase Inhibitory Protein: A Signal Transduction Modulator and Metastasis Suppressor
Forum on Immunopathological Diseases and Therapeutics, Vol.2, 2011, issue 1
Marsha Rich Rosner, Eva M. Eves
Inhibition of Snail-induced Epithelial-Mesenchymal Transition and Induction of the Tumor Metastasis Suppressor Gene Raf-1 Kinase Inhibitor Protein (RKIP) by DETANONOate
Forum on Immunopathological Diseases and Therapeutics, Vol.1, 2010, issue 3
Stavroula Baritaki, Benjamin Bonavida
The Possible Interactions and Therapeutic Roles of Lithium Chloride and Midkine on Cancer Treatment
Critical Reviews™ in Oncogenesis, Vol.24, 2019, issue 1
Ayhan Bilir, Mehmet Yakup Tuna, Ahmet Sükrü Aynacioglu