PXD055563

PXD055563 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-04 13:46:40	ID requested
⏵ 1	2024-10-22 08:02:50	announced

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]

submitter keyword: endochondral ossification, proteomics, multi-omics, phospho-proteomics, transcriptomics,Phlpp2

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD055563

PRIDE project URI

• PRIDE
  1. PXD055563
     1. Label: PRIDE project
     2. Name: Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation