A study of the interaction between MAPKAP Kinase 5 / MK5 and DNAJB1
ForfatterLægreid, Kari Jenssen
The mitogen activated protein kinases (MAPK) are a large and diverse family of protein kinases, contributing to the cells ability to respond to external stimuli by relaying messages in a well orchestrated way until they reach their final destinations. This is achieved through successive phosphorylation events. One member of this large family is mitogen activated protein kinase activated protein kinase 5 (MAPKAPK5/MK5), which is activated by the upstream atypical MAPKs extracellular signal-regulated kinases 3 and 4 (ERK3 and ERK4), and possibly also the conventional MAPK p38MAPK. MK5 has been shown to be implicated in F-actin rearrangement through phosphorylation of heat shock protein 27 (HSP27), tumor suppression through at least two different pathways and cell cycle arrest in response to energy depletion. There has been done relatively little research on this protein, and few bona fide substrates for MK5 are known, although knowledge is emerging. One possible interaction partner for MK5 is DNAJB1, which has been shown to be phosphorylated by MK5 in vitro. DNAJB1 is a member of the heat shock protein 40 (HSP40) family/DNAJ family, which is a subunit of the much larger heat shock protein superfamily. Heat shock proteins mostly function as chaperones and co-chaperones in the cell, assisting in the maintenance of protein homeostasis, by refolding or degrading misfolded proteins. Conditions of stress in the cell can lead to increased levels of misfolded proteins, which in turn are thought to initiate the increased transcription of heat shock proteins observed in stressed cells. DNAJB1 mainly serves as a co-chaperone for heat shock protein 70, and has been implicated to play a role in various types of cancer and neurodegenerative disorders. In this study we demonstrated that MK5 phosphorylates DNAJB1 in vitro, and that Tyrosine residue 6 and Serine residues 149, 151 and 171 in DNAJB1 are in vitro phosphorylation sites for MK5. Our results also indicate that other phosphorylation sites may be present. Further experiments are needed to elucidate the in vivo potential of these phosphoacceptor sites. We also found that MK5 and DNAJB1 exist in complexes. This interaction proved hard to reproduce, indicating that it might be of a transient nature, or perhaps a product of non-physiological conditions. We also showed that both proteins localize mainly to the nucleus in resting cells, when ectopically expressed, and that DNAJB1 seems to downregulate the level or the transcriptional activity of MK5 when both proteins are ectopically expressed in the cell.
ForlagUniversitetet i Tromsø
University of Tromsø
Følgende lisensfil er knyttet til denne innførselen:
Viser innførsler relatert til tittel, forfatter og emneord.
Determinants of Staphylococcus aureus Colonization and Infection. “Exploring the Role of Cell Wall Anchored Proteins in Adhesion and Immune Evasion” Ajayi, Clement (Doctoral thesis; Doktorgradsavhandling, 2018-11-09)Staphylococcus aureus is an efficient human colonizer and pathogen. S.aureus' ability to colonize and/or cause infections in humans is due to its expression of many virulence factors. These virulence factors aid the bacterium in adhering, invading and evading the host´s immune defences. This study focused on exploring the role of two cell wall anchored proteins: Serine-aspartate containing protein ...
Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma : VEGF-A Impact Is Strongly Associated with Ang-2 Andersen, Sigve; Dønnem, Tom; Al-Shibli, Khalid Ibrahim; Al-Saad, Samer; Stenvold, Helge; Busund, Lill-Tove; Bremnes, Roy M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and ...
Humant papillomavirus : en litteraturstudie om HPV, dets relasjon til cancer og tiltak mot videre spredning av virus Gabrielsen, Endre (Master thesis; Mastergradsoppgave, 2012-06-01)I 1983 oppdaget zur Hausen sammenhengen mellom Humant Papillomavirus (HPV) og livmorhalskreft. På denne tiden visste man ikke at det var HPV som var årsaken til at Helaceller kunne leve in vitro. Ny forskning relaterer HPV til en rekke andre cancertyper. En stor andel anal-, oropharyngeal-, penis-, vaginal-, og vulvacancer skyldes HPV. Det er også påvist HPV i tumorvev fra øsofagus, larynx, lunge, ...