The Drosophila midkine/pleiotrophin homologues Miple1 and Miple2 affect adult lifespan but are dispensable for alk signaling during embryonic gut formation

Fredrik Hugosson; Camilla Sjögren; Anna Birve; Ludmilla Hedlund; Therese Eriksson; Ruth H Palmer

doi:10.1371/journal.pone.0112250

The Drosophila midkine/pleiotrophin homologues Miple1 and Miple2 affect adult lifespan but are dispensable for alk signaling during embryonic gut formation

PLoS One. 2014 Nov 7;9(11):e112250. doi: 10.1371/journal.pone.0112250. eCollection 2014.

Authors

Fredrik Hugosson¹, Camilla Sjögren¹, Anna Birve¹, Ludmilla Hedlund¹, Therese Eriksson¹, Ruth H Palmer²

Affiliations

¹ Department of Molecular Biology, Umeå University, Umeå, Sweden.
² Department of Molecular Biology, Umeå University, Umeå, Sweden; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Göteborg, Sweden.

Abstract

Midkine (MDK) and Pleiotrophin (PTN) are small heparin-binding cytokines with closely related structures. The Drosophila genome harbours two genes encoding members of the MDK/PTN family of proteins, known as miple1 and miple2. We have investigated the role of Miple proteins in vivo, in particular with regard to their proposed role as ligands for the Alk receptor tyrosine kinase (RTK). Here we show that Miple proteins are neither required to drive Alk signaling during Drosophila embryogenesis, nor are they essential for development in the fruit fly. Additionally we show that neither MDK nor PTN can activate hALK in vivo when ectopically co-expressed in the fly. In conclusion, our data suggest that Alk is not activated by MDK/PTN related growth factors Miple1 and Miple 2 in vivo.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anaplastic Lymphoma Kinase
Animals
Carrier Proteins / metabolism
Cytokines / genetics
Cytokines / metabolism*
Drosophila / embryology*
Drosophila / genetics
Drosophila / growth & development
Drosophila / physiology*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Female
Gene Deletion
Gene Expression Regulation, Developmental
Humans
Male
Midkine
Receptor Protein-Tyrosine Kinases / metabolism*
Signal Transduction*

Substances

Carrier Proteins
Cytokines
Drosophila Proteins
Miple1 protein, Drosophila
Miple2 protein, Drosophila
pleiotrophin
Midkine
ALK protein, human
Anaplastic Lymphoma Kinase
Receptor Protein-Tyrosine Kinases

Grants and funding

This work has been supported by grants from the Swedish Cancer Society, http://www.cancerfonden.se/, (Grant number 12-0796 to RHP); the Children's Cancer Foundation, http://www.barncancerfonden.se/, (Grant number 13/049 to RHP); the Swedish Research Council, http://www.vr.se/, (Grant number 621-2011-5181 to RHP); and the Lions Cancer Society, Umea, http://www.cancerforskningsfond-umea.lions.se/, (Grant number LP 12-1946 to RHP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.