scholarly journals Cellular Functions of Mitogen-activated Protein Kinases and Protein Tyrosine Phosphatases in Ovarian Granulosa Cells

2004 ◽  
Vol 50 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Mariko TAMURA ◽  
Yosimi NAKAGAWA ◽  
Hidehisa SHIMIZU ◽  
Noriaki YAMADA ◽  
Takashi MIYANO ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Granulosa Cells ◽  
Protein Tyrosine Phosphatases ◽  
Tyrosine Phosphatases ◽  
Cellular Functions ◽  
Mitogen Activated Protein Kinases ◽  
Protein Tyrosine ◽  
Ovarian Granulosa Cells ◽  
Mitogen Activated Protein

scholarly journals Differential Regulation of the Cell Wall Integrity Mitogen-Activated Protein Kinase Pathway in Budding Yeast by the Protein Tyrosine Phosphatases Ptp2 and Ptp3

1999 ◽  
Vol 19 (11) ◽  
pp. 7651-7660 ◽  
Author(s):  
Christopher P. Mattison ◽  
Scott S. Spencer ◽  
Kurt A. Kresge ◽  
Ji Lee ◽  
Irene M. Ota
Keyword(s):  
Cell Wall ◽  
Protein Tyrosine Phosphatases ◽  
Negative Regulator ◽  
Cell Wall Integrity ◽  
Dependent Manner ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Growth Defects ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein kinases (MAPKs) are inactivated by dual-specificity and protein tyrosine phosphatases (PTPs) in yeasts. InSaccharomyces cerevisiae, two PTPs, Ptp2 and Ptp3, inactivate the MAPKs, Hog1 and Fus3, with different specificities. To further examine the functions and substrate specificities of Ptp2 and Ptp3, we tested whether they could inactivate a third MAPK, Mpk1, in the cell wall integrity pathway. In vivo and in vitro evidence indicates that both PTPs inactivate Mpk1, but Ptp2 is the more effective negative regulator. Multicopy expression of PTP2, but not PTP3, suppressed growth defects due to the MEK kinase mutation, BCK1-20, and the MEK mutation,MKK1-386, that hyperactivate this pathway. In addition, deletion of PTP2, but not PTP3, exacerbated growth defects due to MKK1-386. Other evidence supported a role for Ptp3 in this pathway. Expression of MKK1-386 was lethal in the ptp2Δ ptp3Δ strain but not in either single PTP deletion strain. In addition, the ptp2Δ ptp3Δ strain showed higher levels of heat stress-induced Mpk1-phosphotyrosine than the wild-type strain or strains lacking either PTP. The PTPs also showed differences in vitro. Ptp2 was more efficient than Ptp3 at binding and dephosphorylating Mpk1. Another factor that may contribute to the greater effectiveness of Ptp2 is its subcellular localization. Ptp2 is predominantly nuclear whereas Ptp3 is cytoplasmic, suggesting that active Mpk1 is present in the nucleus. Last, PTP2 but not PTP3 transcript increased in response to heat shock in a Mpk1-dependent manner, suggesting that Ptp2 acts in a negative feedback loop to inactivate Mpk1.

scholarly journals Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases

2006 ◽  
Vol 395 (3) ◽  
pp. 483-491 ◽  
Author(s):  
Jeyanthy Eswaran ◽  
Jens Peter von Kries ◽  
Brian Marsden ◽  
Emma Longman ◽  
Judit É. Debreczeni ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Phosphorylation Site ◽  
Protein Tyrosine Phosphatases ◽  
Salt Bridge ◽  
Specific Protein ◽  
Tyrosine Phosphatases ◽  
Selective Inhibitors ◽  
Crystal Forms ◽  
Protein Tyrosine ◽  
Mitogen Activated Protein

Protein tyrosine phosphatases PTPN5, PTPRR and PTPN7 comprise a family of phosphatases that specifically inactivate MAPKs (mitogen-activated protein kinases). We have determined high-resolution structures of all of the human family members, screened them against a library of 24000 compounds and identified two classes of inhibitors, cyclopenta[c]quinolinecarboxylic acids and 2,5-dimethylpyrrolyl benzoic acids. Comparative structural analysis revealed significant differences within this conserved family that could be explored for the design of selective inhibitors. PTPN5 crystallized, in two distinct crystal forms, with a sulphate ion in close proximity to the active site and the WPD (Trp-Pro-Asp) loop in a unique conformation, not seen in other PTPs, ending in a 310-helix. In the PTPN7 structure, the WPD loop was in the closed conformation and part of the KIM (kinase-interaction motif) was visible, which forms an N-terminal aliphatic helix with the phosphorylation site Thr66 in an accessible position. The WPD loop of PTPRR was open; however, in contrast with the structure of its mouse homologue, PTPSL, a salt bridge between the conserved lysine and aspartate residues, which has been postulated to confer a more rigid loop structure, thereby modulating activity in PTPSL, does not form in PTPRR. One of the identified inhibitor scaffolds, cyclopenta[c]quinoline, was docked successfully into PTPRR, suggesting several possibilities for hit expansion. The determined structures together with the established SAR (structure–activity relationship) propose new avenues for the development of selective inhibitors that may have therapeutic potential for treating neurodegenerative diseases in the case of PTPRR or acute myeloblastic leukaemia targeting PTPN7.

scholarly journals Heat Stress Activates the Yeast High-Osmolarity Glycerol Mitogen-Activated Protein Kinase Pathway, and Protein Tyrosine Phosphatases Are Essential under Heat Stress

2002 ◽  
Vol 1 (2) ◽  
pp. 163-173 ◽  
Author(s):  
Astrid Winkler ◽  
Christopher Arkind ◽  
Christopher P. Mattison ◽  
Anne Burkholder ◽  
Kathryn Knoche ◽  
...  
Keyword(s):  
Heat Stress ◽  
Protein Kinase ◽  
Protein Tyrosine Phosphatases ◽  
Mitogen Activated Protein Kinase ◽  
Tyrosine Phosphatases ◽  
High Osmolarity ◽  
Protein Tyrosine ◽  
High Osmolarity Glycerol ◽  
Mitogen Activated Protein ◽  
Stress Activation

ABSTRACT The yeast high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway has been characterized as being activated solely by osmotic stress. In this work, we show that the Hog1 MAPK is also activated by heat stress and that Sho1, previously identified as a membrane-bound osmosensor, is required for heat stress activation of Hog1. The two-component signaling protein, Sln1, the second osmosensor in the HOG pathway, was not involved in heat stress activation of Hog1, suggesting that the Sho1 and Sln1 sensors discriminate between stresses. The possible function of Hog1 activation during heat stress was examined, and it was found that the hog1Δ strain does not recover as rapidly from heat stress as well as the wild type. It was also found that protein tyrosine phosphatases (PTPs) Ptp2 and Ptp3, which inactivate Hog1, have two functions during heat stress. First, they are essential for survival at elevated temperatures, preventing lethality due to Hog1 hyperactivation. Second, they block inappropriate cross talk between the HOG and the cell wall integrity MAPK pathways, suggesting that PTPs are important for maintaining specificity in MAPK signaling pathways.

scholarly journals New Insights into the p38γ and p38δ MAPK Pathways

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ana Risco ◽  
Ana Cuenda
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Protein Kinases ◽  
Expression Patterns ◽  
Cellular Functions ◽  
Mitogen Activated Protein Kinases ◽  
Pathological Conditions ◽  
Mitogen Activated Protein ◽  
Distinct Role ◽  
Made In

The mammalian p38 mitogen-activated protein kinases (MAPKs) family is composed of four members (p38α, p38β, p38γ, and p38δ), which are very similar in amino acid sequence but differ in their expression patterns. This suggests that they may have specific functions in different organs. In the last years most of the effort has been centred on the study of the function of the p38α isoform, which is widely referred to as p38 in the literature. However, the role that other p38 isoforms play in cellular functions and their implication in some of the pathological conditions have not been precisely defined so far. In this paper we highlight recent advances made in defining the functions of the two less studied alternative p38MAPKs, p38γ and p38δ. We describe that these p38MAPKs show similarities to the classical p38α isoform, although they may play central and distinct role in certain physiological and pathological processes.

Sign in / Sign up

Export Citation Format

Share Document