PXD003797

PXD003797 is an original dataset announced via ProteomeXchange.

Title	Analysis of CNK1-SAM domain phosphorylation sites
Description	Scaffold proteins such as CNK1 are hubs for coordinating signalling pathways. Here, we demonstrate that CNK1 is a crucial transducer of growth factor-stimulated and oncogenic signalling. Activation of CNK1 depends on its dimerization executed by the N-terminal sterile motif alpha (SAM) domain. Accordingly, a CNK1 mutant lacking the SAM domain prevents CNK1-driven cell proliferation and matrix metalloproteinase 14 promoter activation. We identified phosphorylation of Ser22 by AKT as trigger for CNK1 dimerisation. Consistently, the mutant CNK1S22D mimicking constitutive phosphorylation stimulates CNK1 signalling, whereas the phosphoylation-dead mutant CNK1S22A does not. Searching the COSMIC database revealed Ser22 as target for oncogenic activation of CNK1. The mutant CNK1S22D and the oncogenic mutant CNK1S22F form clusters in serum-starved cells comparable to clusters of CNK1 in growth factor stimulated cells. Light-activatable CNK1, optoCNK1, based on the light-induced oligomerisation of cryptochrome 2 confirms that dimerization is the trigger for CNK1 activation. CNK1 dimers induced by activating Ser22 mutants or by light enhance cell invasion and ADP ribosylation factors 1 signalling associated with tumour formation. Positive and negative feedback mechanisms regulates CNK1 dimerisation and in this way its activity. Oncogenic mutants of CNK1 support the positive feedback while escape from negative feedback regulation.
HostingRepository	PRIDE
AnnounceDate	2022-02-23
AnnouncementXML	Submission_2022-02-23_09:11:12.064.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Friedel Drepper
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-16 06:01:10	ID requested
⏵ 1	2022-02-23 09:11:12	announced

Dataset with its publication pending

curator keyword: Biological

submitter keyword: CNK1 AKT in vitro kinase EGF stimulation

Bettina Warscheid
contact affiliation	Funktionelle Proteomics Albert-Ludwigs-Universität Freiburg Institut für Biologie II Schänzlestraße 1 79104 Freiburg
contact email	bettina.warscheid@biologie.uni-freiburg.de
lab head
Friedel Drepper
contact affiliation	AG Warscheid Biologie II Albert-Ludwigs-Universität Freiburg Schänzlestr. 1 79104 Freiburg Germany
contact email	friedel.drepper@biologie.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003797
     1. Label: PRIDE project
     2. Name: Analysis of CNK1-SAM domain phosphorylation sites