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Amy L. Stiegler
Yale University
Molecular biologyChemistryMutationIntegrin-linked kinaseBiology
27Publications
10H-index
803Citations
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Publications 32
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#1Rachel Jaber Chehayeb (Yale University)
#2Jessica K. Wang (Yale University)H-Index: 1
Last. Titus J. Boggon (Yale University)H-Index: 47
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The Src homology 2 (SH2) domain has a highly conserved architecture that recognizes linear phosphotyrosine motifs and is present in a wide range of signaling pathways across different evolutionary taxa. A hallmark of SH2 domains is the arginine residue in the conserved "FLVR" motif that forms a direct salt bridge with bound phosphotyrosine. Here, we solve the X-ray crystal structures of the C-terminal SH2 domain of p120RasGAP (RASA1) in its apo and peptide-bound form. We find that the arginine r...
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#2Amy L. StieglerH-Index: 10
Last. Titus J. BoggonH-Index: 47
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The Rho and Ras pathways play vital roles in cell growth, division and motility. Cross-talk between the pathways amplifies their roles in cell proliferation and motility and its dysregulation is involved in disease pathogenesis. One important interaction for cross-talk occurs between p120RasGAP (RASA1), a GTPase activating protein (GAP) for Ras, and p190RhoGAP (p190RhoGAP-A, ARHGAP35), a GAP for Rho. The binding of these proteins is primarily mediated by two SH2 domains within p120RasGAP engagin...
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#2Amy L. StieglerH-Index: 10
Last. Titus J. BoggonH-Index: 47
view all 3 authors...
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#2Amy L. StieglerH-Index: 10
Last. Titus J. BoggonH-Index: 47
view all 3 authors...
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#2Amy L. StieglerH-Index: 10
Last. Titus J. BoggonH-Index: 47
view all 3 authors...
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#1Luca Zammataro (Yale University)H-Index: 16
#2Salvatore Lopez (Yale University)H-Index: 14
Last. Alessandro D. Santin (Yale University)H-Index: 31
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The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs)...
2 CitationsSource
#1Andreas Brodehl (Libin Cardiovascular Institute of Alberta)H-Index: 9
#2Saman Rezazadeh (Libin Cardiovascular Institute of Alberta)H-Index: 1
Last. Brenda Gerull (Libin Cardiovascular Institute of Alberta)H-Index: 21
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Arrhythmogenic cardiomyopathy is a genetic heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes leading to life-threatening ventricular arrhythmias, heart failure, and sudden cardiac death. Mutations in genes encoding cardiac junctional proteins are known to cause about half of cases, while remaining genetic causes are unknown. Using exome sequencing, we identified 2 missense variants (p.H33N and p.H77Y) that were predicted to be damaging in the integrin-linked kinase...
1 CitationsSource
#1Amy L. Stiegler (Yale University)H-Index: 10
#2Titus J. Boggon (Yale University)H-Index: 47
Pseudoenzymes generally lack detectable catalytic activity despite adopting the overall protein fold of their catalytically competent counterparts, indeed ‘pseudo’ family members seem to be incorporated in all enzyme classes. The small GTPase enzymes are important signaling proteins, and recent studies have identified many new family members with noncanonical residues within the catalytic cleft, termed pseudoGTPases. To illustrate recent discoveries in the field, we use the p190RhoGAP proteins a...
2 CitationsSource
#1Amy L. Stiegler (Yale University)H-Index: 10
#2Titus J. Boggon (Yale University)H-Index: 47
Summary The pseudoGTPases are a rapidly growing and important group of pseudoenzymes. p190RhoGAP proteins are critical regulators of Rho signaling and contain two previously identified pseudoGTPase domains. Here we report that p190RhoGAP proteins contain a third pseudoGTPase domain, termed N-GTPase. We find that GTP constitutively purifies with the N-GTPase domain, and a 2.8-A crystal structure of p190RhoGAP-A co-purified with GTP reveals an unusual GTP-Mg 2+ binding pocket. Six inserts in N-GTP...
3 CitationsSource
#1Amy L. StieglerH-Index: 10
#2Titus J. BoggonH-Index: 47
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