A paper containing data fudged by former University of California San Francisco grad student Peter Littlefield has been corrected. We knew that this was coming — last month, the Office of Research Integrity issued a report that Littlefield had admitted to misconduct, and agreed to a retraction or correction of the two affected papers.
Published in Science Signaling, “Structural analysis of the /HER3 heterodimer reveals the molecular basis for activating HER3 mutations” examined the structural details of a protein associated with cancer. It has been cited two times, according to Thomson Scientific’s Web of Knowledge.
According to the correction note, the concentration of a protein presented in one figure was “miscalculated;” in another figure, the error bars were “calculated incorrectly.”
A statement from the UCSF affirmed that principle investigator Natalie Jura has “not been implicated in any research misconduct finding,” and explains that
Dr. Jura and colleagues redid the relevant experiments reported in the Science Signaling paper, and based on that work the editors of Science Signaling published an erratum rather than retracting the paper, concluding that “[n]one of these errors affect the conclusions of the published paper.”
The erratum (behind a paywall – tsk tsk) elaborates:
In the manuscript “Structural analysis of the EGFR/HER3 heterodimer reveals the molecular basis for activating HER3 mutations,” several errors in data were noted by the authors and have been corrected.The errors occurred in data presented in Figs. 5B, 6C, and 6D.
Figure 5B: In the data presented in the original figure, the concentration of the Q790R HER3 mutant protein relative to that of the wild-type HER3 and the S827I mutant was miscalculated and therefore, the concentration of the Q790R mutant was not the same as that of wild-type HER3 and the S827I mutant. These experiments were repeated with an accurately calculated concentration of Q790R and the data in Fig. 5B has been corrected to show these results. The revised data sustain the original conclusion that neither mutation enhanced HER3 allosteric activity in the absence of the juxtamembrane segment-mediated interaction.
The authors also report that the experiments shown in Figs. 5C and 5D were also repeated and produced identical results as those published in the paper.
Figure 6C: In the data presented in the original figure, the wild-type and E909G HER3 mutant constructs had longer N-terminal (extra 21 residues) and C-terminal (extra 11 residues) tags than were reported in the Materials and Methods. The extra sequences originate from the cloning vector and are not known to encode functional peptides. These experiments were repeated using the shorter HER3 constructs matching the sequences reported in the Materials and Methods. As with the longer constructs, the results obtained with the shorter constructs support the conclusion that the E909G mutation increased the dimerization affinity and the catalytic rate of the HER3/EGFR heterodimer.
Km in the presence of the longer E909G HER3 mutant: 0.43 +/− 0.05 μM
Km in the presence of the shorter E909G HER mutant: 0.40 +/− 0.15 μM
Vmax in the presence of the longer E909G HER3 mutant: 3.25 +/− 0.09 s−1
Vmax in the presence of the shorter E909G HER3 mutant: 2.1 +/− 0.18 s−1
Km in the presence of the longer wild-type HER3 construct: 2.2 +/− 0.14 μM
Km in the presence of the shorter wild-type HER3 construct: 1.58 +/− 0.53 μM
Vmax in the presence of the longer wild-type HER3 construct: 1.83 +/− 0.04 s−1
Vmax in the presence of the shorter wild-type HER3 construct: 1.13 +/− 0.11 s−1
The figure has been updated to show the data with the shorter constructs.
Figure 6D: The error bars were calculated incorrectly. The experiments were repeated and the correct statistical analysis was performed. The new results showed that the allosteric activation of the kinase activity EGFR was significantly enhanced by HER3 mutants E687A or E710A compared to that by wild-type HER3 (p values <0.0005), which is the same conclusion obtained with the original incorrect figure. The figure has been corrected.
None of these errors affect the conclusions of the published paper.
The PDF and HTML (full text) have been corrected.
A UCSF spokesperson sent us a statement from Theresa O’Lonergan, Associate Vice Chancellor and Research Integrity Officer. The statement explains that it remains unknown whether the second paper in question will be retracted or corrected, and that no other papers from Jura’s lab are affected by the misconduct.
Here’s the full statement:
Dr. Natalia Jura, assistant professor in the Cardiovascular Research Institute and the Department of Cellular and Molecular Pharmacology at UC San Francisco (UCSF), and principal investigator on the grants that supported Peter Littlefield’s research, has not been implicated in any research misconduct finding by the U.S. Department of Health and Human Services Office of Research Integrity (ORI) or by UCSF.
Dr. Jura immediately and appropriately notified the University after Mr. Littlefield revealed to her that he had falsified and fabricated data in papers published in Science Signaling and Chemistry & Biology, and she has fully cooperated with ORI’s investigation.
Mr. Littlefield also cooperated with ORI’s investigation, and ORI’s findings of misconduct were based on UCSF’s assessment, Mr. Littlefield’s admission, and ORI’s own analysis. UCSF found no evidence that any other papers from the Jura laboratory have been affected by Mr. Littlefield’s misconduct.
As a condition of the Voluntary Settlement Agreement between Mr. Littlefield, ORI, and UCSF, Mr. Littlefield agreed to “retraction or correction” of the two papers. Dr. Jura and colleagues redid the relevant experiments reported in the Science Signaling paper, and based on that work the editors of Science Signaling published an erratum rather than retracting the paper, concluding that “[n]one of these errors affect the conclusions of the published paper.” The editors of Chemistry & Biology have not yet determined a course of action.
We’ve contacted Jura. A spokesperson for Cell Press, which publishes Chemistry & Biology, told us
We have no updates at this time.
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