Oncotarget

Research Papers:

The microdomain-organizing protein MPP1 is required for insulin-stimulated activation of H-Ras

Joanna Podkalicka, Agnieszka Biernatowska, Paulina Olszewska, Sabina Tabaczar and Aleksander F. Sikorski _

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Oncotarget. 2018; 9:18410-18421. https://doi.org/10.18632/oncotarget.24847

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Abstract

Joanna Podkalicka1,*, Agnieszka Biernatowska1,*, Paulina Olszewska1, Sabina Tabaczar1 and Aleksander F. Sikorski1

1Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, 50–383 Wrocław, Poland

*These Authors contributed equally to this work

Correspondence to:

Aleksander F. Sikorski, email: [email protected]

Keywords: small GTPases; H-Ras; PM-lateral organization; MPP1

Received: August 31, 2017     Accepted: February 27, 2018     Published: April 06, 2018

ABSTRACT

Signaling complexes are localized to distinct plasma-membrane domains which undergo precise spatiotemporal regulation. A crucial link between membrane dynamics and the small GTPase, H-Ras, has been suggested, connecting membrane localization, clustering and scaffolding with its activity and signal transduction. Results of this study suggest a relationship between MPP1 and/or MPP1-dependent plasma-membrane organization and H-Ras activation. Namely, we show here that in HEL cells, MPP1 knock-down lead to the disruption of signaling cascade(s) from the activated insulin receptor. The signal inhibition occurred at the level of H-Ras, as it showed impaired GDP-to-GTP exchange and further interaction with its effector molecule, Raf. Moreover, in these cells H-Ras detergent-resistant membrane localization was not sensitive to insulin treatment which may imply molecular mechanism via which MPP1 affects functions of other proteins which may be connected with functional domain formation. Understanding the link between MPP1 and activation of H-Ras, may provide an important insight into the complexity of Ras related signaling pathways which may become a potential target for associated cancer therapies.


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