التفاصيل البيبلوغرافية
| العنوان: |
Mal connects TLR2 to PI3Kinase activation and phagocyte polarization. |
| المؤلفون: |
Sierra, Sandra Santos1, Deshmukh, Sachin D.1, Kalnitski, Julia1, Peter Küenzi2, Wymann, Matthias P.3, Golenbock, Douglas T.4, Henneke, Philipp1 philipp.henneke@uniklinik-freiburg.de |
| المصدر: |
EMBO Journal. 7/8/2009, Vol. 28 Issue 14, p2018-2027. 10p. 2 Diagrams, 6 Graphs. |
| مصطلحات موضوعية: |
*LIPOPROTEINS, *PHAGOCYTES, *CELLS, *IMMUNE system, *BACTERIAL diseases |
| مستخلص: |
The recognition of bacterial lipoproteins by toll-like receptor (TLR) 2 is pivotal for inflammation initiation and control in many bacterial infections. TLR2-dependent signalling is currently believed to essentially require both adaptor proteins MyD88 (myeloid differentiation primary response gene 88) and Mal/TIRAP (MyD88-adapter-like/TIR-domain-containing adaptor protein). TLR2-dependent, but MyD88-independent responses have not been described yet. We report here on a novel-signalling pathway downstream of TLR2, which does not adhere to the established model. On stimulation of the TLR2/6 heterodimer with diacylated bacterial lipoproteins, Mal directly interacts with the regulatory subunit of phosphoinositide 3-kinase (PI3K), p85α, in an inducible fashion. The Mal–p85α interaction drives PI3K-dependent phosphorylation of Akt, phosphatidylinositol(3,4,5)P3 (PIP3) generation and macrophage polarization. MyD88 is not essential for PI3K activation and Akt phosphorylation; however, cooperates with Mal for PIP3 formation and accumulation at the leading edge. In contrast to TLR2/6, TLR2/1 does not require Mal or MyD88 for Akt phosphorylation. Hence, Mal specifically connects TLR2/6 to PI3K activation, PIP3 generation and macrophage polarization. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder