| 1. |
- Heldin, Carl-Henrik, et al.
(författare)
-
Signals and Receptors
- 2016
-
Ingår i: Cold Spring Harbor Perspectives in Biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- Communication between cells in a multicellular organism occurs by the production of ligands (proteins, peptides, fatty acids, steroids, gases, and other low-molecular-weight compounds) that are either secreted by cells or presented on their surface, and act on receptors on, or in, other target cells. Such signals control cell growth, migration, survival, and differentiation. Signaling receptors can be single-span plasma membrane receptors associated with tyrosine or serine/threonine kinase activities, proteins with seven transmembrane domains, or intracellular receptors. Ligand-activated receptors convey signals into the cell by activating signaling pathways that ultimately affect cytosolic machineries or nuclear transcriptional programs or by directly translocating to the nucleus to regulate transcription.
|
|
| 2. |
- Heldin, Carl-Henrik, 1952-, et al.
(författare)
-
Signals and receptors
- 2014
-
Ingår i: Signal transduction. - New York : Cold Spring Harbor Laboratory Press (CSHL). - 9780879699017 ; , s. 3-29
-
Bokkapitel (refereegranskat)
|
|
| 3. |
- Honjo, Yasuyuki, et al.
(författare)
-
TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma
- 2007
-
Ingår i: Cell Cycle. - 1551-4005. ; 6:11, s. 1360-1366
-
Tidskriftsartikel (refereegranskat)abstract
- We generated a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (T beta RI) floxed mice with neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/ or perianal regions. Transplantation of these tumors into athymic nude mice resulted in 62% tumorigenicity. To determine whether evasion of the immune response plays any role in this tumorigenesis, we analyzed the expression levels of receptors for interleukin-13 (mIL-13R), a key negative regulator of tumor immunosurveillance, and found that 33% of COKO tumors expressed the IL-13R alpha 2 chain. Primary cultures of the SCCs expressing IL-13R alpha 2 were sensitive to the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first demonstration that loss of T beta RI can lead to spontaneous tumor formation. These mice can serve as a unique mouse model of SCC to evaluate the tumorigenicity and effect of anti-cancer therapeutics.
|
|
| 4. |
- Hou, Xu, et al.
(författare)
-
PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets
- 2010
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:27, s. 12216-12221
-
Tidskriftsartikel (refereegranskat)abstract
- The importance of identifying VEGF-independent pathways in pathological angiogenesis is increasingly recognized as a result of the emerging drug resistance to anti-VEGF therapies. PDGF-CC is the third member of the PDGF family discovered after more than two decades of studies on PDGF-AA and PDGF-BB. The biological function of PDGF-CC and the underlying cellular and molecular mechanisms remain largely unexplored. Here, using different animal models, we report that PDGF-CC inhibition by neutralizing antibody, shRNA, or genetic deletion suppressed both choroidal and retinal neovascularization. Importantly, we revealed that PDGF-CC targeting acted not only on multiple cell types important for pathological angiogenesis, such as vascular mural and endothelial cells, macrophages, choroidal fibroblasts and retinal pigment epithelial cells, but also on the expression of other important angiogenic genes, such as PDGF-BB and PDGF receptors. At a molecular level, we found that PDGF-CC regulated glycogen synthase kinase (GSK)-3beta phosphorylation and expression both in vitro and in vivo. Activation of GSK3beta impaired PDGF-CC-induced angiogenesis, and inhibition of GSK3beta abolished the antiangiogenic effect of PDGF-CC blockade. Thus, we identified PDGF-CC as an important candidate target gene for antiangiogenic therapy, and PDGF-CC inhibition may be of therapeutic value in treating neovascular diseases.
|
|
