• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding.

The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk) acts as an intermediate in protein kinase C-regulated TrkA cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (TACE) is phosphorylated by Erk at threonine 735. In addition, we show that Erk and TACE associate. This association is favored by Erk activation and by the presence of threonine 735. In contrast to the Erk route, the p38 MAPK was able to stimulate TrkA cleavage in cells devoid of TACE activity, indicating that other proteases are also involved in TrkA shedding. These results demonstrate that secretases are able to discriminate between the different stimuli that trigger membrane protein ectodomain cleavage and indicate that phosphorylation by MAPKs may regulate the proteolytic function of membrane secretases.

Pubmed ID: 12058067

Authors

  • Díaz-Rodríguez E
  • Montero JC
  • Esparís-Ogando A
  • Yuste L
  • Pandiella A

Journal

Molecular biology of the cell

Publication Data

June 11, 2002

Associated Grants

None

Mesh Terms

  • ADAM Proteins
  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Metalloendopeptidases
  • Mitogen-Activated Protein Kinases
  • Phosphorylation
  • Protein Kinase C
  • Receptor, trkA
  • Restriction Mapping
  • Retroviridae
  • Tetradecanoylphorbol Acetate
  • Threonine
  • Transfection