PXD010246

PXD010246 is an original dataset announced via ProteomeXchange.

Title	Human testis phosphoproteome reveals kinases as potential targets in spermatogenesis and testicular cancer
Description	Spermatogenesis is a complex cell differentiation process that includes marked genetic, cellular functional and structural changes. It requires tight regulation, since disturbances in any of the spermatogenic stages would lead to fertility deficiencies. In order to increase our knowledge of signal transduction during sperm development, we carried out a large-scale identification of the phosphorylation events that occur in the human gonad. Metal oxide affinity chromatography using TiOx combined with LC-MS/MS was conducted to profile the phosphoproteome of human testes with full spermatogenesis. A total of 8187 phosphopeptides derived from 2661 proteins were identified, resulting in the most complete report of human testicular phosphoproteins to date. Phosphorylation events were enriched in proteins functionally related to spermatogenesis, as well as to highly active processes in the male gonad, such as transcriptional and translational regulation, cytoskeleton organization, DNA packaging, cell cycle and apoptosis. Moreover, 174 phosphorylated kinases were identified. The most active and abundant human protein kinases in the testis were predicted both by the phosphorylation status of the kinase activation loop and the number of phosphopeptide spectra identified. The potential function of two of those kinases, cyclin-dependent kinase 12 (CDK12) and p21-activated kinase 4(PAK4), has been explored by protein-protein interaction analysis, immunodetection in human and mouse testicular tissue, and functional assay in a human embryonal carcinoma cell line. The co-localization of CDK12 with Golgi markers and probably pro-acrosomal vesicles suggests a potential crucial role of this protein kinase in sperm formation. PAK4 expression has been found limited to human spermatogonia, and a role in embryonal carcinoma cell response to apoptosis has been observed. Together, our data confirm that phosphoregulation by protein kinases is highly active in sperm differentiation, and open a window to detailed characterization and validation of potential targets for the development of drugs modulating male fertility, and tumor behavior.
HostingRepository	PRIDE
AnnounceDate	2019-02-01
AnnouncementXML	Submission_2019-02-01_11:20:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sander Piersma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-27 03:57:05	ID requested
⏵ 1	2019-02-01 11:20:08	announced

Castillo J, Knol JC, Korver CM, Piersma SR, Pham TV, de Goeij-de Haas RR, van Pelt AMM, Jimenez CR, Jansen BJH, Human Testis Phosphoproteome Reveals Kinases as Potential Targets in Spermatogenesis and Testicular Cancer. Mol Cell Proteomics, 18(Suppl 1):S132-S144(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Human, testis, phosphokinase ranking, label-free, single-shot, phosphoproteomics

Connie Ramona Jimenez
contact affiliation	OncoProteomics Laboratory, Dept of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
contact email	c.jimenez@vumc.nl
lab head
Sander Piersma
contact affiliation	OncoProteomics Laboratory, dept of Medical Oncology, VUmc Medical Center, Amsterdam, The Netherlands
contact email	s.piersma@vumc.nl
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/2019/02/PXD010246

PRIDE project URI

• PRIDE
  1. PXD010246
     1. Label: PRIDE project
     2. Name: Human testis phosphoproteome reveals kinases as potential targets in spermatogenesis and testicular cancer