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Exp Cell Res. 2015 Jul 1;335(1):115-22. doi: 10.1016/j.yexcr.2015.04.019. Epub 2015 May 7.

PKA and CDK5 can phosphorylate specific serines on the intracellular domain of podoplanin (PDPN) to inhibit cell motility.

Author information

1
Graduate School of Biomedical Sciences and Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Science Center, 2 Medical Center Drive, Stratford, NJ 08084, USA.
2
Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
3
Center for Advanced Proteomics Research and Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School Cancer Center,205 S. Orange Avenue, F-1226, Newark, NJ 07103, USA.
4
Department of Physiology and Biophysics, Basic Science Tower T-5, Stony Brook University, Stony Brook, NY 11794-8661, USA.
5
Graduate School of Biomedical Sciences and Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Science Center, 2 Medical Center Drive, Stratford, NJ 08084, USA. Electronic address: gary.goldberg@rowan.edu.

Abstract

Podoplanin (PDPN) is a transmembrane glycoprotein that promotes tumor cell migration, invasion, and cancer metastasis. In fact, PDPN expression is induced in many types of cancer. Thus, PDPN has emerged as a functionally relevant cancer biomarker and chemotherapeutic target. PDPN contains 2 intracellular serine residues that are conserved between species ranging from mouse to humans. Recent studies indicate that protein kinase A (PKA) can phosphorylate PDPN in order to inhibit cell migration. However, the number and identification of specific residues phosphorylated by PKA have not been defined. In addition, roles of other kinases that may phosphorylate PDPN to control cell migration have not been investigated. We report here that cyclin dependent kinase 5 (CDK5) can phosphorylate PDPN in addition to PKA. Moreover, results from this study indicate that PKA and CDK5 cooperate to phosphorylate PDPN on both intracellular serine residues to decrease cell motility. These results provide new insight into PDPN phosphorylation dynamics and the role of PDPN in cell motility. Understanding novel mechanisms of PDPN intracellular signaling could assist with designing novel targeted chemotherapeutic agents and procedures.

KEYWORDS:

Cell migration; Cyclin dependent Kinase 5; Podoplanin; Protein Kinase A; Serine phosphorylation

PMID:
25959509
PMCID:
PMC4556139
DOI:
10.1016/j.yexcr.2015.04.019
[Indexed for MEDLINE]
Free PMC Article

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