Faculty Collaboration Database

Differential regulation of the dual-specificity protein-tyrosine phosphatases CL100, B23, and PAC1 in mesangial cells. J Am Soc Nephrol 1997 Jan;8(1):40-50

Date

01/01/1997

Pubmed ID

9013447

DOI

10.1681/ASN.V8140

Scopus ID

2-s2.0-0030699487 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

The extracellular-signal-regulated kinase (ERK), the best described MAP kinase cascade, is a major signaling system by which cells transduce extracellular cues into intracellular responses. ERK is activated by phosphorylation both on tyrosine and threonine residues. Therefore, a new clas of protein-tyrosine phosphatases (PTPases) that exhibit dual catalytic activity toward both regulatory sites on ERK is of special interest in the control of intracellular signaling. This study examined the expression and regulation of the dual-specificity PTPases CL100, B23, and PAC1. Findings included differential expression of these phosphatases in diverse cell lines and an expression of all three dual-specificity PTPases in human mesangial cells (HMC), thereby allowing investigation of their regulation in a single cell line. The MEK antagonist PD 098059 and selective extracellular agonists of ERK were used to demonstrate the induction of CL100, PAC1, and B23 in response to activation of the ERK cascade. In contrast, anisomycin, an agonist of the recently described MAP kinases stress-activated protein kinase (SAPK) and p38 MAP kinase, stimulated CL100 gene expression but had little effect on PAC1 and B23. This effect of anisomycin was partly inhibited in the presence of the p38 MAP kinase antagonist SB 203580. This study suggests a potential mechanism to regulate ERK activity through feedback inhibition by demonstrating the ERK cascade's induction of the dual-specificity PTPases CL100, PAC1, and B23. Moreover, this study suggests an ERK-independent induction of CL100 following stimulation of SAPK and p38 MAP kinase. This mode of induction of a phosphatase capable of inactivating ERK may play an important role in the cellular stress response.

Author List

Bokemeyer D, Sorokin A, Dunn MJ

Author

Andrey Sorokin PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anisomycin
Cell Cycle Proteins
Cell Line
Dual Specificity Phosphatase 1
Dual Specificity Phosphatase 2
Enzyme Inhibitors
Flavonoids
Gene Expression Regulation, Enzymologic
Glomerular Mesangium
Humans
Imidazoles
Immediate-Early Proteins
Male
Nuclear Proteins
Phosphoprotein Phosphatases
Protein Phosphatase 1
Protein Phosphatase 2
Protein Tyrosine Phosphatases
Pyridines
RNA, Messenger
Rats
Rats, Sprague-Dawley
Signal Transduction