Publication Date:
2000-01-05
Description:
The mitogen-activated protein (MAP) kinase cascade is inactivated at the level of MAP kinase by members of the MAP kinase phosphatase (MKP) family, including MKP-1. MKP-1 was a labile protein in CCL39 hamster fibroblasts; its degradation was attenuated by inhibitors of the ubiquitin-directed proteasome complex. MKP-1 was a target in vivo and in vitro for p42(MAPK) or p44(MAPK), which phosphorylates MKP-1 on two carboxyl-terminal serine residues, Serine 359 and Serine 364. This phosphorylation did not modify MKP-1's intrinsic ability to dephosphorylate p44(MAPK) but led to stabilization of the protein. These results illustrate the importance of regulated protein degradation in the control of mitogenic signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brondello, J M -- Pouyssegur, J -- McKenzie, F R -- GM26939/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2514-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de Valombrose, Nice 06189, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617468" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blood
;
*Cell Cycle Proteins
;
Cell Division
;
Cell Line
;
Cricetinae
;
Culture Media
;
Cysteine Endopeptidases/metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Dual Specificity Phosphatase 1
;
Estradiol/pharmacology
;
Humans
;
Immediate-Early Proteins/chemistry/*metabolism
;
Leucine/analogs & derivatives/pharmacology
;
Leupeptins/pharmacology
;
MAP Kinase Signaling System
;
Mitogen-Activated Protein Kinase 1/*metabolism
;
Mitogen-Activated Protein Kinase 3
;
Mitogen-Activated Protein Kinases/*metabolism
;
Multienzyme Complexes/metabolism
;
Mutation
;
Nitrophenols/metabolism
;
Organophosphorus Compounds/metabolism
;
*Phosphoprotein Phosphatases
;
Phosphorylation
;
Proteasome Endopeptidase Complex
;
Protein Phosphatase 1
;
Protein Tyrosine Phosphatases/chemistry/*metabolism
;
Ubiquitins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
