GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:25007873

From GONUTS
Jump to: navigation, search
Citation

Obeidat, M, Li, L and Ballermann, BJ (2014) TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells. Am. J. Physiol. Renal Physiol. 307:F623-33

Abstract

The function of TIMAP, an endothelial cell (EC)-predominant protein phosphatase 1-regulatory subunit, is poorly understood. We explored the potential role of TIMAP in the Akt-dependent regulation of glomerular EC proliferation, survival, and in vitro angiogenesis. To deplete TIMAP, the EC were transfected with TIMAP-specific or nonspecific small interfering (si) RNA. The rate of electrical impedance development across subconfluent EC monolayers, a measure of the time-dependent increase in EC number, was 93 ± 2% lower in TIMAP-depleted than in control EC. This effect on cell proliferation was associated with reduced DNA synthesis and increased apoptosis: TIMAP silencing reduced 5-ethynyl-2'-deoxyuridine incorporation by 38 ± 2% during the exponential phase of EC proliferation, and cleaved caspase 3 as well as caspase 3 activity increased in TIMAP-depleted relative to control cells. Furthermore, TIMAP depletion inhibited the formation of angiogenic sprouts by glomerular EC in three-dimensional culture. TIMAP depletion strongly diminished growth factor-stimulated Akt phosphorylation without altering ERK1/2 phosphorylation, suggesting a specific effect on the PI3K/Akt/PTEN pathway. Endogenous TIMAP and PTEN colocalized in EC and coimmunoprecipitated from EC lysates. The inhibitory PTEN phosphorylation on S370 was significantly reduced in TIMAP-depleted compared with control EC, while phosphorylation of PTEN on the S380/T382/T383 cluster remained unchanged. Finally, the PTEN inhibitor bpV(phen) fully reversed the suppressive effect of TIMAP depletion on Akt phosphorylation. The data indicate that in growing EC, TIMAP is necessary for Akt-dependent EC proliferation, survival, and angiogenic sprout formation and that this effect of TIMAP is mediated by inhibition of the tumor suppressor PTEN.

Links

PubMed Online version:10.1152/ajprenal.00070.2014

Keywords

Apoptosis/physiology; Cell Proliferation/physiology; Cell Survival/physiology; Cells, Cultured; Endothelial Cells/cytology; Endothelial Cells/physiology; Humans; In Vitro Techniques; Kidney Glomerulus/cytology; Kidney Glomerulus/physiology; Membrane Proteins/physiology; Neovascularization, Physiologic/physiology; PTEN Phosphohydrolase/antagonists & inhibitors; PTEN Phosphohydrolase/physiology; Phosphatidylinositol 3-Kinases/physiology; Phosphorylation/physiology; Proto-Oncogene Proteins c-akt/antagonists & inhibitors; Proto-Oncogene Proteins c-akt/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PTEN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96T49

F

Seeded From UniProt

complete

HUMAN:PTEN

located_in

GO:0042995: cell projection

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0002188)

Seeded From UniProt

complete

HUMAN:PP16B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P60484

F

Seeded From UniProt

complete

HUMAN:PP16B

involved_in

GO:0014066: regulation of phosphatidylinositol 3-kinase signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002188)

Seeded From UniProt

complete

HUMAN:PP16B

located_in

GO:0042995: cell projection

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0002188)

Seeded From UniProt

complete

HUMAN:PP16B

involved_in

GO:0001938: positive regulation of endothelial cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002188)

Seeded From UniProt

complete

HUMAN:PP16B

involved_in

GO:1902309: negative regulation of peptidyl-serine dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002188)
  • has_input:(UniProtKB:P31749)

Seeded From UniProt

complete

HUMAN:PP16B

involved_in

GO:1903589: positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0002188)

Seeded From UniProt

complete

HUMAN:PTEN

part_of

GO:0042995: cell projection

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0002188)

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.