Serines in the intracellular tail of podoplanin (PDPN) regulate cell motility

Harini Krishnan, Jhon A. Ochoa-Alvarez, Yongquan Shen, Evan Nevel, Meenakshi Lakshminarayanan, Mary C. Williams, Maria I. Ramirez, W. Todd Miller, Gary S. Goldberg

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Podoplanin (PDPN) is a transmembrane receptor that affects the activities of Rho, ezrin, and other proteins to promote tumor cell motility, invasion, and metastasis. PDPN is found in many types of cancer and may serve as a tumor biomarker and chemotherapeutic target. The intracellular region of PDPN contains only two serines, and these are conserved in mammals including mice and humans. We generated cells from the embryos of homozygous null Pdpn knock-out mice to investigate the relevance of these serines to cell growth and migration on a clear (PDPN-free) background. We report here that one or both of these serines can be phosphorylated by PKA (protein kinase A). We also report that conversion of these serines to nonphosphorylatable alanine residues enhances cell migration, whereas their conversion to phosphomimetic aspartate residues decreases cell migration. These results indicate that PKA can phosphorylate PDPN to decrease cell migration. In addition, we report that PDPN expression in fibroblasts causes them to facilitate the motility and viability of neighboring melanoma cells in coculture. These findings shed new light on how PDPN promotes cell motility, its role in tumorigenesis, and its utility as a functionally relevant biomarker and chemotherapeutic target.

Original languageEnglish (US)
Pages (from-to)12215-12221
Number of pages7
JournalJournal of Biological Chemistry
Volume288
Issue number17
DOIs
StatePublished - Apr 26 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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