A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanisms (2018)

Antenucci, L., Hytönen, V. P., & Ylänne, J. (2018). Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanisms. Journal of Biological Chemistry, 293(13), 4591-4602. https://doi.org/10.1074/jbc.RA117.000660

JYU-tekijät tai -toimittajat

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Antenucci, Lina; Hytönen, Vesa P.; Ylänne, Jari

Lehti tai sarja: Journal of Biological Chemistry

ISSN: 0021-9258

eISSN: 1067-8816

Julkaisuvuosi: 2018

Volyymi: 293

Lehden numero: 13

Artikkelin sivunumerot: 4591-4602

Kustantaja: American Society for Biochemistry and Molecular Biology

Julkaisumaa: Yhdysvallat (USA)

Julkaisun kieli: englanti

DOI: https://doi.org/10.1074/jbc.RA117.000660

Julkaisun avoin saatavuus: Ei avoin

Julkaisukanavan avoin saatavuus: 

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/57653

Tiivistelmä

Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues. In addition to its immunoreceptor function, Syk is activated downstream of integrin pathways, and integrins bind to the same region in Syk as does pITAM. However, it is unknown whether integrins and pITAM use the same mechanism to activate Syk. Here, using purified Syk protein and fluorescence-based enzyme assay we investigated whether interaction of the integrin β3 cytoplasmic domain with the Syk regulatory domain causes changes in Syk activity similar to those induced by pITAM peptides. We observed no direct Syk activation by soluble integrin peptide, and integrin did not compete with pITAM-induced activation even though at high concentrations, the integrin cytoplasmic domain peptide competed with Syk's substrate. However, clustered integrin peptides induced Syk activation, presumably via a transphosphorylation mechanism. Moreover, the clustered integrins also activated a Syk variant in which tyrosines were replaced with phenylalanine (Y348F/Y352F), indicating that clustered integrin–induced Syk activation involved other phosphorylation sites. In conclusion, integrin cytoplasmic domains do not directly induce Syk conformational changes and do not activate Syk via the same mechanism as pITAM.

YSO-asiasanat: entsyymit; kinaasit; soluviestintä; integriinit

Vapaat asiasanat: enzyme kinetics; integrin; spleen tyrosine kinase (Syk); surface plasmon resonance (SPR)

Liittyvät organisaatiot

Hankkeet, joissa julkaisu on tehty

OKM-raportointi: Kyllä

Raportointivuosi: 2018

JUFO-taso: 1