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

Krishnan, Harini; Retzbach, Edward P.; Ramirez, María I.; Liu, Tong; Li, Hong; Miller, W. Todd; Goldberg, Gary S.

doi:10.1016/j.yexcr.2015.04.019

Cited by 25 publications

(42 citation statements)

References 44 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While PKA can phosphorylate either of the 2 serines (S167 or S171 in mouse PDPN), CDK5 preferably phosphorylates the C-terminal serine (S171 in mouse PDPN). 4 These data suggest a scenario in which PKA and CDK5 work together to phosphorylate the intracellular serines of PDPN in order to inhibit cell motility. Reagents that can induce PDPN phosphorylation may be used to inhibit tumor motility.…”

Section: Podoplanin As a Can Cer Biomarkermentioning

confidence: 88%

“…The kinases that can phosphorylate PDPN cytoplasmic serine residues were identified as protein kinase A (PKA) and cyclin‐dependent kinase 5 (CDK5), as shown in Figure . While PKA can phosphorylate either of the 2 serines (S167 or S171 in mouse PDPN), CDK5 preferably phosphorylates the C‐terminal serine (S171 in mouse PDPN) . These data suggest a scenario in which PKA and CDK5 work together to phosphorylate the intracellular serines of PDPN in order to inhibit cell motility.…”

Section: Targeting the Intracellular Podoplanin Domainmentioning

confidence: 91%

“…Interestingly, phosphorylation of serines inhibits PDPN‐mediated cell migration. Furthermore, both serines need to be phosphorylated to inhibit cell migration . Phosphorylation can modify the structural conformation of amino acids in the PDPN intracellular domain, as shown in Figure .…”

Section: Targeting the Intracellular Podoplanin Domainmentioning

confidence: 99%

“…Reagents that can induce PDPN phosphorylation may be used to inhibit tumor motility. For example, 8‐br‐cAMP, disulfiram and CARP‐1 functional mimetics have been shown to induce PDPN phosphorylation and inhibit PDPN‐mediated cell migration . Thus, PDPN may be targeted both on its intracellular domain as well as its extracellular domain to inhibit cell migration.…”

Section: Targeting the Intracellular Podoplanin Domainmentioning

confidence: 99%

“…These ligands and binding partners interact with PDPN to control tumor cell migration, invasion and metastasis. [1][2][3][4] Podoplanin expression is induced by tumor promoters including TPA, RAS and Src. [5][6][7] For example, the Src tyrosine kinase utilizes the focal adhesion adaptor protein Cas/BCAR1 to induce PDPN expression to promote tumor cell motility.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Podoplanin: An emerging cancer biomarker and therapeutic target

et al. 2018

Self Cite

View full text Add to dashboard Cite

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR‐T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.

show abstract

Section: Podoplanin As a Can Cer Biomarkermentioning

confidence: 88%

Section: Targeting the Intracellular Podoplanin Domainmentioning

confidence: 91%

Section: Targeting the Intracellular Podoplanin Domainmentioning

confidence: 99%

Section: Targeting the Intracellular Podoplanin Domainmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Podoplanin: An emerging cancer biomarker and therapeutic target

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration

Retzbach

Sheehan

Krishnan

et al. 2022

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

The Src tyrosine kinase is a strong tumor promotor. Over a century of research has elucidated fundamental mechanisms that drive its oncogenic potential. Src phosphorylates effector proteins to promote hallmarks of tumor progression. For example, Src associates with the Cas focal adhesion adaptor protein to promote anchorage independent cell growth. In addition, Src phosphorylates Cas to induce Pdpn expression to promote cell migration. Pdpn is a transmembrane receptor that can independently increase cell migration in the absence of oncogenic Src kinase activity. However, to our knowledge, effects of Src kinase activity on anchorage independent cell growth and migration have not been examined in the absence of Pdpn expression. Here, we analyzed the effects of an inducible Src kinase construct in knockout cells with and without exogenous Pdpn expression on cell morphology migration and anchorage independent growth. We report that Src promoted anchorage independent cell growth in the absence of Pdpn expression. In contrast, Src was not able to promote cell migration in the absence of Pdpn expression. In addition, continued Src kinase activity was required for cells to assume a transformed morphology since cells reverted to a nontransformed morphology upon cessation of Src kinase activity. We also used phosphoproteomic analysis to identify 28 proteins that are phosphorylated in Src transformed cells in a Pdpn dependent manner. Taken together, these data indicate that Src utilizes Pdpn to promote transformed cell growth and motility in complementary, but parallel, as opposed to serial, pathways.

show abstract