PXD024650

PXD024650 is an original dataset announced via ProteomeXchange.

Title	Highly multiplexed kinase profiling in spleen with targeted mass spectrometry reveals kinome plasticity across species
Description	Early attrition of drug candidates, including kinase inhibitors, often occurs due to issues that arise during preclinical safety and efficacy evaluation. This problem may be exacerbated by the fact that these studies might fail to consider the basic physiological differences which could exist between human patients and animal models. Little is currently known about how kinase expression can vary between species, and tools to quantitatively measure such differences are lacking. We report the development of a targeted mass spectrometry-based assay capable of monitoring >50 different kinases using peptides conserved in humans and the key preclinical species used in drug development (mouse, rat, dog and cynomolgus monkey). These methods were then used to profile inter-species kinome variability in spleen with three of the current techniques used in targeted proteomics (MRM, PRM and IS-PRM). IS-PRM provided the highest number of kinase identifications, and the results indicate that while this initial set of kinases exhibits high correlation between species for this tissue type, discreet species-specific differences do exist, especially within the cyclin-dependent kinase (CDK) family. Understanding these differences could help rationalize the findings of preclinical studies and have major implications for the selection of these animals as models in kinase drug development.
HostingRepository	PanoramaPublic
AnnounceDate	2021-08-19
AnnouncementXML	Submission_2021-08-19_08:53:12.950.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Laura Marholz
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090; scientific name: Canis lupus familiaris; NCBI TaxID: 9615; scientific name: Rattus norvegicus; NCBI TaxID: 10116; scientific name: Macaca fascicularis; NCBI TaxID: 9541; scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	TSQ Altis; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-10 13:45:06	ID requested
1	2021-07-28 15:30:28	announced
⏵ 2	2021-08-19 08:53:13	announced	: Added PubMed Id

Marholz LJ, Federspiel JD, Suh H, Fernandez Ocana M, Highly Multiplexed Kinase Profiling in Spleen with Targeted Mass Spectrometry Reveals Kinome Plasticity across Species. J Proteome Res, 20(9):4272-4283(2021) [pubmed]

submitter keyword: Kinase, spleen, preclinical species

Mireia Fernandez Ocana
contact affiliation	Pfizer
contact email	Mireia.FernandezOcana@pfizer.com
lab head
Laura Marholz
contact affiliation	Pfizer
contact email	laura.marholz@pfizer.com
dataset submitter

Panorama Public dataset URI