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.


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*


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

Grant support

This work has been supported by grants from the Swedish Cancer Society,, (Grant number 12-0796 to RHP); the Children's Cancer Foundation,, (Grant number 13/049 to RHP); the Swedish Research Council,, (Grant number 621-2011-5181 to RHP); and the Lions Cancer Society, Umea,, (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.