[27] Properties and use of H-series compounds as protein kinase inhibitors

Hidaka, Hiroyoshi; Watanabe, Masato; Kobayashi, Ryōji

doi:10.1016/0076-6879(91)01029-2

Cited by 122 publications

(84 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CREB phosphorylation in response to forskolin, CPTcAMP, and the PKA inhibitor mirrored that of ERK. These results support our earlier studies (25) with the PKA inhibitor H89 (45,46) and confirm that the majority of FSH-stimulated ERK activation in this granulosa cell model is PKA-dependent.…”

Section: Fsh-stimulated Erk Activationsupporting

confidence: 81%

Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase

Cottom¹,

Salvador²,

Maizels³

et al. 2003

Journal of Biological Chemistry

125

115

View full text Add to dashboard Cite

In this report we sought to elucidate the mechanism by which the follicle-stimulating hormone (FSH) receptor signals to promote activation of the p42/p44 extracellular signal-regulated protein kinases (ERKs) in granulosa cells. Results show that the ERK kinase MEK and upstream intermediates Raf-1, Ras, Src, and L-type Ca 2؉ channels are already partially activated in vehicletreated cells and that FSH does not further activate them. This tonic stimulatory pathway appears to be restrained at the level of ERK by a 100-kDa phosphotyrosine phosphatase that associates with ERK in vehicletreated cells and promotes dephosphorylation of its regulatory Tyr residue, resulting in ERK inactivation. FSH promotes the phosphorylation of this phosphotyrosine phosphatase and its dissociation from ERK, relieving ERK from inhibition and resulting in its activation by the tonic stimulatory pathway and consequent translocation to the nucleus. Consistent with this premise, FSH-stimulated ERK activation is inhibited by the cell-permeable protein kinase A-specific inhibitor peptide Myr-PKI as well as by inhibitors of MEK, Src, a Ca 2؉ channel blocker, and chelation of extracellular Ca 2؉ . These results suggest that FSH stimulates ERK activity in immature granulosa cells by relieving an inhibition imposed by a 100-kDa phosphotyrosine phosphatase.The cytoplasmic p42/p44 mitogen-activated protein kinase (MAPK) 1 /extracellular signal-regulated kinases (ERKs) comprise a critical convergence point in the signaling pathways initiated by a variety of receptor agonists that promote cellular differentiation or proliferation. For the classic receptor tyrosine kinase-initiated pathway, growth factors like epidermal growth factor (EGF) induce the autophosphorylation of their receptors and create specific binding sites for Src homology 2-containing proteins such as Grb2 (1). Grb2 complexed to Sos associates with the receptor tyrosine kinase, and Sos stimulates GDP release from Ras, leading to Ras activation. Active Ras then binds to Raf-1, leading to its activation, and Raf-1 in turn catalyzes the serine phosphorylation and activation of the MAPK/ERK kinase MEK. MEK then catalyzes the phosphorylation of ERK on regulatory Thr and Tyr residues, resulting in ERK activation.Guanine nucleotide-binding protein-coupled receptors (GPCRs) are also well known activators of ERK; however, there are a variety of pathways by which GPCRs promote ERK activation. Often, GPCRs such as those activated by lysophosphatidic acid or angiotensin II promote the transactivation of a receptor tyrosine kinase as evidenced by its increased tyrosine phosphorylation (2). Receptor tyrosine kinase transactivation directs the tyrosine phosphorylation of adaptor proteins such as Shc, recruitment of the Grb2-Sos complex, and subsequent Ras activation. It is less clear how GPCRs promote the tyrosine phosphorylation of the receptor tyrosine kinase, although Src activation downstream of the G␤␥ has been implicated in some cells (3, 4). For those GPCRs whose activated G␣ subunits promote...

show abstract

Section: Fsh-stimulated Erk Activationsupporting

confidence: 81%

Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase

Cottom¹,

Salvador²,

Maizels³

et al. 2003

Journal of Biological Chemistry

125

115

View full text Add to dashboard Cite

show abstract

“…The canonical phosphorylation pathway is mediated by cAMPdependent protein kinase (PKA), which induces phosphorylase kinase activation, the enzyme that phosphorylates PYG (53). To determine whether the canonical pathway mediated activation of PYG in response to IL-2, we pretreated the cells with H89 (50 M), a pharmacological inhibitor of PKA (36), and stimulated cells for 10 min with IL-2 or forskolin (10 M; an activator of adenylate cyclase) (37). Forskolin induced glycogen phosphorylase activation via the PKA-mediated canonical activation pathway, which was blocked by the pretreatment with H89 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation

Arrizabalaga

Lacerda

Zubiaga

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Rac1 has a relevant role in signal transduction pathways in T lymphocytes. Results: Rac1 GTPase associates with glycogen phosphorylase and modulates its enzymatic activity to trigger T cell proliferation. Conclusion: This study reveals a new role for Rac1 GTPase in cellular physiology, coordinating metabolism and proliferation. Significance: This new Rac1/PYGM pathway might be essential for an appropriate immune response.

show abstract

“…The isoquinoline sulfonamides H7 and H8 are derivatives of naphthalene sulfonamides but have the naphthalene ring replaced by isoquinoline (Hidaka et al, 1984(Hidaka et al, , 1991. On basis of their different inhibitory constants (K i ) for PK-A and PK-C, it is possible to differentiate between their effects on each of the 2 protein kinases.…”

Section: Gel Electrophoresismentioning

confidence: 99%