PXD002031

PXD002031 is an original dataset announced via ProteomeXchange.

Title	Tec kinase deficiency in macrophages
Description	Previous work has shown conflicting roles for Tec family kinases in regulation of Toll-like receptor (TLR)-dependent signalling in myeloid cells. In the present study, we performed a detailed investigation of the role of Btk and Tec kinases in regulating TLR signalling in several types of primary murine macrophages. We demonstrate that primary resident peritoneal macrophages deficient for Btk and Tec secrete less pro-inflammatory cytokines in response to TLR stimulation than wild type cells. In contrast, we found that bone marrow-derived and thioglycollate-elicited peritoneal macrophages deficient for Btk and Tec secrete more pro-inflammatory cytokines than wild type cells. We then compared the phosphoproteome regulated by Tec kinases and lipopolysaccharide in primary peritoneal and bone marrow derived macrophages. From this analysis we determined that Tec kinases regulate different signalling programs in these cell types. In additional studies using bone marrow-derived macrophages, we find that Tec and Btk promote phosphorylation events necessary for immunoreceptor-mediated inhibition of TLR signalling. Taken together, our results are consistent with a model where Tec kinases (Btk, Tec, Bmx) are required for TLR-dependent signalling in many types of myeloid cells. However, our data also support a cell type-specific TLR-inhibitory role for Btk and Tec that is mediated by immunoreceptor activation and signalling via PI3K.
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_07:47:12.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Richard James
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-09 01:14:51	ID requested
⏵ 1	2018-10-24 07:47:13	announced

Tampella G, Kerns HM, Niu D, Singh S, Khim S, Bosch KA, Garrett ME, Moguche A, Evans E, Browning B, Jahan TA, Nacht M, Wolf-Yadlin A, Plebani A, Hamerman JA, Rawlings DJ, James RG, The Tec Kinase-Regulated Phosphoproteome Reveals a Mechanism for the Regulation of Inhibitory Signals in Murine Macrophages. J Immunol, 195(1):246-56(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Tec kinase macrophage

Richard Goff James
contact affiliation	Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA USA
contact email	rickerj@u.washington.edu
lab head
Richard James
contact affiliation	Seattle Children's Research Institute
contact email	rickerj@u.washington.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002031
     1. Label: PRIDE project
     2. Name: Tec kinase deficiency in macrophages