PXD055563 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation |
Description | Appendicular skeletal growth and bone mass acquisition are controlled by a variety of growth factors, hormones, and mechanical forces in a dynamic process called endochondral ossification. In long bones, chondrocytes in the growth plate proliferate and undergo hypertrophy to drive bone lengthening and mineralization. Pleckstrin homology (PH) domain and leucine rich repeat phosphatase 1 and 2 (Phlpp1 and Phlpp2) are serine/threonine protein phosphatases that regulate cell proliferation, survival, and maturation via Akt, PKC, Raf1, S6k, and other intracellular signaling cascades. Germline deletion of Phlpp1 suppresses bone lengthening in part through parathyroid hormone receptor-dependent signaling in growth plate chondrocytes. Here, we demonstrate that Phlpp2 does not regulate endochondral ossification, and we define the molecular differences between Phlpp1 and Phlpp2 in chondrocytes. Phlpp2-/- mice are phenotypically indistinguishable from their wildtype (WT) littermates, with similar bone length, bone mass, and growth plate dynamics. Deletion of Phlpp2 had moderate effects on the chondrocyte transcriptome and proteome compared to WT cells. By contrast, Phlpp1/2-/- (double knockout) mice resembled Phlpp1-/- mice phenotypically and chondrocyte phospho-proteomes of Phlpp1-/- and Phlpp1/2-/- chondrocytes were different than WT and Phlpp2-/- chondrocyte phospho-proteomes. Data integration via multiparametric analysis identified alterations in Pdpk1 and Pak1/2 signaling pathways in chondrocytes lacking Phlpp1. In conclusion, these data demonstrate that Phlpp1, but not Phlpp2, regulates endochondral ossification through multiple and complex signaling cascades. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_08:02:49.248.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD055563 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Benjamin Madden |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-09-04 13:46:40 | ID requested | |
⏵ 1 | 2024-10-22 08:02:50 | announced | |
Publication List
10.1016/j.bone.2024.117265; |
10.6019/PXD055563; |
Weaver SR, Peralta-Herrera E, Torres HM, Jessen E, Bradley EW, Westendorf JJ, Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation. Bone, 189():117265(2024) [pubmed] |
Keyword List
submitter keyword: endochondral ossification, proteomics, multi-omics, phospho-proteomics, transcriptomics,Phlpp2 |
Contact List
Dr. Jennifer Westendorf Ph.D. |
contact affiliation | Department of Orthopedic Surgery, Mayo Clinic, Rochester MN USA |
contact email | westendorf.jennifer@mayo.edu |
lab head | |
Benjamin Madden |
contact affiliation | Mayo Clinic |
contact email | madden.benjamin@mayo.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD055563
- Label: PRIDE project
- Name: Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation