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A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2 总被引:1,自引:0,他引:1
Cébe Suarez S Pieren M Cariolato L Arn S Hoffmann U Bogucki A Manlius C Wood J Ballmer-Hofer K 《Cellular and molecular life sciences : CMLS》2006,63(17):2067-2077
The development of functional blood and lymphatic vessels requires spatio-temporal coordination of the production and release
of growth factors such as vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in multiple isoforms
with distinct biological properties and bind to three types of VEGF receptors. A VEGF-A splice variant, VEGF-A165b, has recently been isolated from kidney epithelial cells. This variant is identical to VEGF-A165 except for the last six amino acids encoded by an alternative exon. VEGF-A165b and VEGF-A165 bind VEGF receptors 1 and 2 with similar affinity. VEGF-A165b elicits drastically reduced activity in angiogenesis assays and even counteracts signaling by VEGF-A165. VEGF-A165b weakly binds to heparan sulfate and does not interact with neuropilin-1, a coreceptor for VEGF receptor 2. To determine
the molecular basis for altered signaling by VEGF-A165b we measured VEGF receptor 2 and ERK kinase activity in endothelial cells in culture. VEGF-A165 induced strong and sustained activation of VEGF receptor 2 and ERK-1 and −2, while activation by VEGF-A165b was only weak and transient. Taken together these data show that VEGF-A165b has attenuated signaling potential through VEGF receptor 2 defining this new member of the VEGF family as a partial receptor
agonist.
Received 31 May 2006; received after revision 26 June 2006; accepted 14 July 2006 相似文献
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The role of VEGF receptors in angiogenesis; complex partnerships 总被引:6,自引:0,他引:6
Cébe-Suarez S Zehnder-Fjällman A Ballmer-Hofer K 《Cellular and molecular life sciences : CMLS》2006,63(5):601-615
Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development and homeostasis but also have
profound effects on neural cells. VEGFs are predominantly produced by endothelial, hematopoietic and stromal cells in response
to hypoxia and upon stimulation with growth factors such as transforming growth factors, interleukins or platelet-derived
growth factor. VEGFs bind to three variants of type III receptor tyrosine kinases, VEGF receptor 1, 2 and 3. Each VEGF isoform
binds to a particular subset of these receptors giving rise to the formation of receptor homo- and heterodimers that activate
discrete signaling pathways. Signal specificity of VEGF receptors is further modulated upon recruitment of coreceptors, such
as neuropilins, heparan sulfate, integrins or cadherins. Here we summarize the knowledge accumulated since the discovery of
these proteins more than 20 years ago with the emphasis on the signaling pathways activated by VEGF receptors in endothelial
cells during cell migration, growth and differentiation.
Received 15 September 2005; received after revision 11 November; accepted 24 November 2005 相似文献
3.
Roth L Koncina E Satkauskas S Crémel G Aunis D Bagnard D 《Cellular and molecular life sciences : CMLS》2009,66(4):649-666
The semaphorin family is a large group of proteins controlling cell migration and axonal growth cone guidance. These proteins
are bi-functional signals capable of growth promotion or growth inhibition. Initially described in the nervous system, the
majority of studies related to semaphorins and semaphorin signalling are nowadays performed in model systems outside the nervous
system. Here, we provide an exhaustive review of the many faces of semaphorins both during developmental, regulatory and pathological
processes. Indeed, because of their crucial fundamental roles, the semaphorins and their receptors represent important targets
for the development of drugs directed at a variety of diseases.
Received 22 August 2008; received after revision 22 September 2008; accepted 24 September 2008
L. Roth, E. Koncina, S. Satkauskas: These authors contributed equally to this work. 相似文献
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