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Biomedical subjects

H Yamashita

Publications and source records attributed to H Yamashita.

At least 19 recordsLinked to original sources
PubMed1999

Oxidation of low density lipoprotein and plasma by 15-lipoxygenase and free radicals.

It is generally accepted that the oxidation of pentadiene structures of polyunsaturated lipids by lipoxygenase (LOX) is regio- and enantio-specific, while the free radical-mediated lipid peroxidation gives stereo-random racemic products. It was confirmed that the oxidation of human low density lipoprotein (LDL) by 15-LOX from rabbit reticulocytes gave phosphatidylcholine (PC) and cholesteryl ester (CE) hydroperoxides regio-, stereo- and enantio-specifically. 15-LOX also oxidized human plasma to give specific PC and CE hydroperoxides in spite of the presence of high concentrations of antioxidants. More CE hydroperoxides were formed than PC hydroperoxides from LDL, but the reverse order was observed for plasma oxidation. The S/R ratio of the hydroperoxides decreased during long time incubation but remained significantly larger than one, while free radical-mediated oxidation of LDL and plasma gave racemic products.

Animals↗
PubMed1999

Antiaggregatory, antithrombotic effects of MS-180, a novel platelet glycoprotein IIb/IIIa receptor antagonist.

The antiaggregatory and antithrombotic effects of (S)-(-)-ethyl[6-[4-(morpholinoformimidoyl)benzamido]-3,4-dihydro-2 H-1-benzo-pyran-3-yl]acetate hydrochloride (MS-180), a novel platelet glycoprotein IIb/IIIa receptor antagonist, were investigated. Ma-HCl, (S)-(-)-[6-[4-(Morpholinoformimidoyl)benzamido]-3,4-dihydro-2H-1-b enzopyran-3-yl]acetic acid hydrochloride, the hydrochloride salt of Ma (active metabolite), inhibited the binding of fibrinogen to immobilized human glycoprotein IIb/III receptor with an IC50 value of 0.12+/-0.03 nM without affecting binding to either fibronectin or vitronectin receptors. In anesthetized guinea pigs, intraduodenal administration of MS-180 caused dose-dependent inhibition of both ADP- and collagen-induced ex vivo platelet aggregation. At the same dosages, occluded thrombus formation and platelet release reactions were also markedly suppressed. In anesthetized dogs, the bleeding time was prolonged slightly even when submaximal inhibition (< 90%) of ex vivo platelet aggregation was achieved following i.v. administration of Ma-HCl. Aspirin (100 mg/kg) prolonged the bleeding time to the same extent as MS-180 (1 mg/kg), although it suppressed only collagen-induced platelet aggregation. Therefore, MS-180 may be clinically useful for the treatment of thrombotic diseases.

Acetates↗
PubMed1999

Down regulation of the prepro-orexin gene expression in genetically obese mice.

The gene expression of prepro-orexin, the precursor of orexin-A and orexin-B which are hypothalamic pepetides that are associated with feeding behavior, were examined in control (C57B1/6J) and obese (ob/ob and db/db) mice using in situ hybridization histochemistry. Orexins are identical with hypocretins that have been identified by directional tag PCR subtractive hybridization method. In situ hybridization histochemistry revealed that the expression of the prepro-orexin gene was significantly decreased in ob/ob and db/db mice compared with control mice. The gene expression of neuropeptide Y (NPY), a potent feeding stimulant, is known to be increased in ob/ob and db/db mice. The expression of the NPY gene in the arcuate nucleus was increased remarkably in ob/ob and db/db mice compared to that of control mice. An immunohistochemical study showed that orexin-A and orexin-B immunoreactive neurons exhibited in the lateral and posterior hypothalamic areas and the perifornical nucleus were distributed similarly in control, ob/ob and db/db mice. These results suggest that the regulatory mechanism of orexins/hypocretins may be different from that of NPY in genetically obese mice.

Animals↗
PubMed1999

Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems.

We determined the immunohistochemical distributions of orexin-A and orexin-B, hypothalamic peptides that function in the regulation of feeding behavior and energy homeostasis. Orexin-A and -B neurons were restricted to the lateral and posterior hypothalamus, whereas both orexin-A and -B nerve fibers projected widely into the olfactory bulb, cerebral cortex, thalamus, hypothalamus, and brainstem. Dense populations of orexin-containing fibers were present in the paraventricular thalamic nucleus, central gray, raphe nuclei, and locus coeruleus. Moderate numbers of these fibers were found in the olfactory bulb, insular, infralimbic and prelimbic cortex, amygdala, ventral, and dorsolateral parts of the suprachiasmatic nucleus, paraventricular nucleus except the lateral magnocellular division, arcuate nucleus, supramammillary nucleus, nucleus of the solitary tract, and dorsal motor nucleus of the vagus. Small numbers of orexin fibers were present in the perirhinal, motor and sensory cortex, hippocampus, and supraoptic nucleus, and a very small number in the lateral magnocellular division of the paraventricular nucleus. Intracerebroventricular injections of orexins induced c-fos expression in the paraventricular thalamic nucleus, locus coeruleus, arcuate nucleus, central gray, raphe nuclei, nucleus of the solitary tract, dorsal motor nucleus of the vagus, suprachiasmatic nucleus, supraoptic nucleus, and paraventricular nucleus except the lateral magnocellular division. The unique neuronal distribution of orexins and their functional activation of neural circuits suggest specific complex roles of the peptides in autonomic and neuroendocrine control.

Animals↗
PubMed1999

Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurones.

1. The expression, distribution and function of P2X purinoceptors in the supraoptic nucleus (SON) were investigated by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and Ca2+-imaging and whole-cell patch-clamp techniques, respectively. 2. RT-PCR analysis of all seven known P2X receptor mRNAs in circular punches of the SON revealed that mRNAs for P2X2, P2X3, P2X4, P2X6 and P2X7 receptors were expressed in the SON, and mRNAs for P2X3, P2X4 and P2X7 were predominant. 3. In situ hybridization histochemistry for P2X3 and P2X4 receptor mRNAs showed that both mRNAs were expressed throughout the SON and in the paraventricular nucleus (PVN). 4. ATP caused an increase in [Ca2+]i in a dose-dependent manner with an ED50 of 1.7 x 10-5 M. The effects of ATP were mimicked by ATPgammaS and 2-methylthio ATP (2MeSATP), but not by AMP, adenosine, UTP or UDP. alphabeta-Methylene ATP (alphabetaMeATP) and ADP caused a small increase in [Ca2+]i in a subset of SON neurones. 5. The P2X7 agonist 2'- & 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) at 10-4 M increased [Ca2+]i, but the potency of BzATP was lower than that of ATP. In contrast, BzATP caused a more prominent [Ca2+]i increase than ATP in non-neuronal cells in the SON. 6. The effects of ATP were abolished by extracellular Ca2+ removal or by the P2 antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), and inhibited by extracellular Na+ replacement or another P2 antagonist, suramin, but were unaffected by the P2X7 antagonist oxidized ATP, and the inhibitor of Ca2+-ATPase in intracellular Ca2+ stores cyclopiazonic acid. 7. Two patterns of desensitization were observed in the [Ca2+]i response to repeated applications of ATP: some neurones showed little or moderate desensitization, while others showed strong desensitization. 8. Whole-cell patch-clamp analysis showed that ATP induced cationic currents with marked inward rectification. The ATP-induced currents exhibited two patterns of desensitization similar to those observed in the [Ca2+]i response. 9. The results suggest that multiple P2X receptors, including P2X3, are functionally expressed in SON neurones, and that activation of these receptors induces cationic currents and Ca2+ entry. Such ionic and Ca2+-signalling mechanisms triggered by ATP may play an important role in the regulation of SON neurosecretory cells.

Adenosine↗
PubMed1999

A pedigree with a novel presenilin 1 mutation at a residue that is not conserved in presenilin 2.

OBJECTIVE: To disclose a novel mutation of the presenilin 1 (PS1) gene responsible for early-onset Alzheimer disease and to clarify genotype-phenotype correlation that should help to establish the function of this protein. BACKGROUND: The PS1 and presenilin 2 (PS2) genes carry missense mutations in families with Alzheimer disease. The PS1 and PS2 proteins have similar structures, and all presently known mutations are in nucleotides coding for amino acids that are conserved between the 2 presenilins. METHODS: Sequence and restriction fragment length polymorphism analyses of PS1 gene of DNA from a pedigree with early-onset Alzheimer disease. RESULTS: Sequence analysis disclosed a novel PS1 mutation in a pedigree of Japanese origin with early-onset Alzheimer disease. This mutation, which is predicted to cause a missense substitution of lysine for glutamic acid, occurred at codon 123 of PS1 that was not a conserved residue in PS2. The 2 patients of this pedigree shared an early clinical phenotype consisting of later-onset, progressive aphasia, but preserved visuospatial ability, which was indistinguishable from those of other PS1-associated Alzheimer disease cases. CONCLUSION: These results demonstrate that a missense mutation in a region not conserved between PS1 and PS2 can cause Alzheimer disease.

Age of Onset↗
PubMed1999

Postoperative tetany in Graves disease: important role of vitamin D metabolites.

OBJECTIVE: To test the authors' hypothesis of the causal mechanism(s) of postoperative tetany in patients with Graves disease. SUMMARY BACKGROUND DATA: Previous studies by the authors suggested that postoperative tetany in patients with Graves disease occurs during the period of bone restoration and resulted from continuation of a calcium flux into bone concomitant with transient hypoparathyroidism induced by surgery. PATIENTS AND METHODS: A prospective study was carried out to investigate sequential changes in serum levels of intact parathyroid hormone (iPTH), calcium and other electrolytes, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D), and bone metabolic markers in 109 consecutive patients with Graves disease who underwent subtotal thyroidectomy. RESULTS: Preoperative serum iPTH levels negatively correlated with ionized calcium levels and positively correlated with 1,25(OH)2D or 1,25(OH)2D/25OHD. After the operation, there was a significant decline in levels of ionized calcium, magnesium, and iPTH. Serum iPTH was not detected in 15 patients after surgery. Four of these 15 patients, and 1 patient whose iPTH level was below normal, developed tetany. Preoperative serum ionized calcium levels were significantly lower, and iPTH levels were higher, in the 5 patients with tetany than in the 11 patients who did not develop tetany despite undetectable iPTH levels. The tetany group had significantly lower serum 25OHD levels and higher 1,25(OH)2D levels, and had increased 1,25(OH)2D/25OHD as an index of the renal 25OHD-1-hydroxylase activity than those in the nontetany group. These results suggest that patients with a high serum level of iPTH as a result of low serum calcium levels (secondary hyperparathyroidism) are susceptible to tetany under conditions of hypoparathyroid function after surgery. CONCLUSIONS: Postoperative tetany occurs in patients with secondary hyperparathyroidism caused by a relative deficiency in calcium and vitamin D because of their increased demand for bone restoration after preoperative medical therapy concomitant with transient hypoparathyroidism after surgery. Calcium and vitamin D supplements may be recommended before and/or after surgery for patients in whom postoperative tetany is expected to develop.

Adolescent↗
PubMed1999

Possible virulence factors of Staphylococcus aureus in a mouse septic model.

Twenty clinical isolates of Staphylococcus aureus were examined to elucidate the virulence factors which are directly related to lethality in a mouse septic model. Heat or formalin treatment of the organism abolished the lethal activity of the live organism during challenge intravenously administered via the tail vein. Nevertheless, injection of ten times concentrated culture supernatant fluid (SUP) showed lethal activity in the mouse. However, there was no lethality when SUP was heated at 60 degrees C for 15 min. To examine variations of SUP lethality among strains, we collected 20 strains of S. aureus from four different hospitals. Then, we compared several factors for SUP lethality, which were the extracellular toxins and enzymes, such as toxic shock syndrome toxin 1, enterotoxin A, B, D, and hemolysins (alpha,beta,gamma), and also cytotoxic activity to human polymorphonuclear leukocytes and Vero cells. No difference was found among these factors except cytotoxic activity to Vero cells. Furthermore, we compared two strains in a mouse septic model according to the grade of bacteremia and lethal events. We found that mortality was higher with challenge by the strain whose SUP was lethal in comparison to the strain whose SUP was not lethal, even though the viable bacteria counts in the septic blood in both strains were not significantly different. This strongly supports the possibility that extracellular products, not the cell wall components, of S. aureus play the key role in the lethal event in this mouse septic model. In addition, among the extracellular products, those which have cytotoxic activity to Vero cells may contribute to the lethality in sepsis caused by S. aureus in this murine model.

Animals↗
PubMed1999

Effects of centrally administered pituitary adenylate cyclase-activating polypeptide on c-fos gene expression and heteronuclear RNA for vasopressin in rat paraventricular and supraoptic nuclei.

The effects of intracerebroventricular (i.c.v.) administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the expression of c-fos gene as well as heteronuclear (hn) RNA for arginine vasopressin (AVP) in paraventricular (PVN) and supraoptic nuclei (SON) of rats were investigated by immunohistochemistry for c-fos protein (Fos) and in situ hybridization histochemistry for c-fos mRNA and AVP hnRNA. The i.c.v. administration of PACAP (200 pmol/rat) caused a marked induction of Fos-like immunoreactivity (LI) in PVN and SON. The nuclear Fos-LI existed in AVP-LI containing cells in the PVN and SON. The expression of the c-fos gene in the PVN and SON was increased in a dose-related manner 30 min after i.c. v. administration of PACAP. PACAP-induced expression of the c-fos gene was significantly reduced by pretreatment with a PACAP receptor antagonist, PACAP-(6-38)-NH2. In addition, Fos-LI and the expression of the c-fos gene were also observed in the periventricular region of the third ventricle after i.c.v. administration of PACAP. The induction of c-fos gene expression in the PVN and SON reached a maximum 30 min after PACAP administration. The expression of c-fos gene in the PVN and SON induced by i.c.v. administration of vasoactive intestinal peptide (200 pmol/rat) was weaker than that induced by PACAP. The hnRNA for AVP in the PVN and SON was significantly increased 30 min after i.c.v. administration of PACAP (200 pmol/rat). Our results suggest that PACAP activates PVN and SON neurons via PACAP receptors and, in parallel, transcription of the AVP gene in the PVN and SON.

Animals↗
PubMed1999

Lack of effect of apolipoprotein E E4 allele on neuropsychiatric manifestations in Alzheimer's disease.

The association between the apolipoprotein E epsilon 4 (APOE E4) allele and a wide spectrum of behavioral symptoms of Alzheimer's disease (AD) was investigated. Neither the severity nor the presence of any behavioral changes was associated with the number of APOE E4 alleles, even after controlling for the effects of age at onset, sex, education level, duration of illness, and severity of dementia. The findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele.

Aged↗
PubMed1999

[Bone morphogenetic protein (BMP) receptors and signal transduction].

BMPs are multifunctional cytokines which regulate cellular proliferation, differentiation, apoptosis of various cell types, including osteoblasts and chondroblasts. These functions are related to various biological functions in vivo; e.g. formation of bone and cartilage, embryogenesis, and organogenesis. BMPs transduce signals through binding to type I and type II receptors with serine/threonine kinase activity. As for type I receptors, BMPs bind to BMP type IA receptor, BMP type IB receptor and activin type I receptor. As for type II receptors, BMPs bind to BMP type II receptor, activin type II receptor and activin type IIB receptor. In the receptor-ligand complexes, type II receptors phosphorylate type I receptors in the GS domain (domain rich in glycine, serine and threonine residues) to activate the latter. The activated type I receptors phosphorylate Smad family, which transduces the signals from cytoplasm into nuclei.

Animals↗
PubMed1999

Hyaluronan synthase expression in bovine eyes.

PURPOSE: Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan, is a component of the extracellular matrix (ECM). It is expressed in eyes and plays important roles in many biologic processes, including cell migration, proliferation, and differentiation. Hyaluronan is produced by HA synthase (HAS), which has three isoforms: HAS1, HAS2, and HAS3. In this study, the HAS expression in the anterior segment of bovine eyes was investigated to determine the significance of HA in eyes. METHODS: To obtain bovine HAS probes, degenerate oligonucleotide primers, based on well-conserved amino acid sequences including the catalytic region of each HAS isoform, were used for reverse transcription-polymerase chain reaction to amplify mRNA from bovine corneal endothelial cells (BCECs). Hyaluronan synthase-1 expression in the anterior segment of bovine eyes at the protein level was investigated by immunohistochemistry. RESULTS: All three HAS isoforms were expressed in BCECs at the mRNA level. Amplified cDNA fragments of HAS1, HAS2, and HAS3 from BCECs can be aligned to human counterparts, showing similarities of 100%, 97.3%, and 100%, respectively, at the amino acid level. Hyaluronan synthase 1 was expressed at the protein level in corneal epithelium, keratocyte, corneal endothelium, conjunctival epithelium, ciliary epithelium, capillary endothelium, and trabecular meshwork. CONCLUSIONS: Hyaluronan synthase isoforms were expressed in the ocular anterior segment and are speculated to be involved in HA production in situ.

Amino Acid Sequence↗
PubMed1998

Purification, cDNA cloning and expression of human NG,NG-dimethylarginine dimethylaminohydrolase.

cDNA encoding N(G),N(G)-dimethylarginine dimethylaminohydrolase from rat kidney had been cloned [Kimoto, M., Sasakawa, T., Tsuji, H., Miyatake, S., Oka, T., Nio, N. & Ogawa, T. (1997) Biochim. Biophys. Acta 1337, 6-10]. The enzyme hydrolyzes N(G),N(G)-dimethyl-L-arginine and N(G)-monomethyl-L-arginine, which are known as endogenous inhibitors for the nitric oxide-generating system. In the present study, human N(G),N(G)-dimethylarginine dimethylaminohydrolase has been purified to homogeneity from liver and characterized. The cDNA clone encoding human N(G),N(G)-dimethylarginine dimethylaminohydrolase was isolated from a human kidney lambda gt10 library using a probe prepared from a plasmid containing the entire coding region of rat N(G),N(G)-dimethylarginine dimethylaminohydrolase. Its open reading frame encoded a protein of 285 amino acids with a molecular mass of 31,121 Da. The deduced amino acid sequence exhibits 93% identity with that of rat. The cDNA was expressed as a fusion protein in Escherichia coli and the recombinant protein exhibited enzyme activity which is the same as that of natural enzyme.

Amidohydrolases↗
PubMed1998

Immunohistochemical analysis of metallothionein in astrocytic tumors in relation to tumor grade, proliferative potential, and survival.

BACKGROUND: Metallothionein (MT) is the name for a family of predominantly intracellular protein thiol compounds involved in anticancer drug resistance. For certain tumors, MT is related to grade of tumor malignancy and prognosis. The authors evaluated the expression of MT in 114 astrocytic tumors in relation to the proliferative potential of tumors and the survival of patients. METHODS: Paraffin embedded tissue sections were stained with monoclonal anti-metallothionein and MIB-1 Ki-67 antibodies by avidin-biotin complex immunohistochemistry. RESULTS: MT expression was observed in 2 of 6 pilocytic astrocytomas, in 10 of 24 Grade 2 astrocytomas, in 16 of 25 anaplastic astrocytomas, and in 47 of 59 glioblastomas. In addition to the tumor cells, microvascular endothelial proliferation and smooth muscle of tumor vessel walls were frequently MT positive. The glioblastomas had a significantly higher percentage of MT positive cells compared with low grade (P < 0.0001) and anaplastic (P < 0.04) astrocytomas. MT expression in astrocytomas had no correlation with tumor recurrence. The mean Ki-67 labeling index (LI) was significantly higher in the high grade (3-4) compared with the low grade (1-2) astrocytomas. MT positive astrocytic tumors had statistically significantly higher mean Ki-67 LI compared with MT negative tumors, irrespective of histologic grade. Although the levels of MT and Ki-67 LI varied in individual tumors, the mean Ki-67 LI increased in parallel to the increasing MT staining grade, and this difference attained statistical significance only for glioblastoma. MT positive anaplastic astrocytoma and glioblastoma patients did not survive as long as the MT negative patients, although this difference attained statistical significance only for anaplastic astrocytoma. CONCLUSIONS: The current study suggests that MT might play a significant role in the growth of astrocytic tumors, with an acquired enhanced ability to produce MT as the malignant potential of a tumor increases.

Adolescent↗
PubMed1998

GABAB receptor-mediated inhibition of spontaneous action potential discharge in rat supraoptic neurons in vitro.

To elucidate the role of GABAB receptors in the regulation of the electrical activity of magnocellular neurons of the supraoptic nucleus (SON), the effects of GABAB agonist and antagonist on the firing rate of spontaneous action potentials were studied in SON slice preparations of rats by extracellular recordings. In the presence of the gamma-amino butyric acid (GABA)-gated chloride channel blocker, picrotoxin, the selective GABAB agonist, baclofen, reduced the firing rate of action potentials in both phasic and non-phasic neurons in a dose-dependent manner. The reduction in the firing rate induced by baclofen was reversed by the selective GABAB antagonist, 2-hydroxy saclofen (2OH-saclofen), also in a dose-dependent manner. In non-phasic neurons, 2OH-saclofen significantly increased the firing rate and the effect was additive to the effect of picrotoxin. In phasic neurons, 2OH-saclofen alone did not increase the firing rate, but it reversed suppression of the firing induced by increasing extracellular Ca2+ concentration to 2.1 mM. Baclofen also reduced the firing rate of non-phasic neurons of virgin and lactating female rats, indicating that the GABAB receptor-mediated inhibition is not confined to SON neurons of male rats. The evidence indicates that activation of GABAB receptors inhibits electrical activity of SON neurons of both male and female rats and that GABAB receptors may play an important role in the inhibitory regulation of the electrical activity of SON neurons by GABA.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Epitope mapping of monoclonal antibodies against 4-aminobenzoate hydroxylase from Agaricus bisporus.

Four monoclonal antibodies (mAbs) against 4-aminobenzoate hydroxylase (EC 1.14.13.27) have been produced (H. Tsuji et al., J. Biol. Chem. 265 (1990) 16064; T. Ogawa et al., Biochim. Biophys. Acta 1115 (1992) 220). Of the mAbs, three mAbs (mAb-A, -B1 and -B2) recognize the FAD-binding domain of the enzyme. In the present study, the epitopes of the mAbs on the enzyme have been examined using pGEX-2T expression systems for DNA fragments encoding various partial amino acid sequences of 4-aminobenzoate hydroxylase. The epitopes for mAb-A, -B1 and -B2 were shown to be on sequences 413-434, 435-460 and 380-413, respectively. These findings suggest that these epitopes for mAb-A, -B1 and -B2 may be close to the isoalloxazine moiety of FAD, which plays a central role in the catalysis of the enzyme.

Agaricus↗
PubMed1998

Differential control of the phosphorylation state of proline-juxtaposed serine residues Ser725 of Stat5a and Ser730 of Stat5b in prolactin-sensitive cells.

Transcription factors of the Stat family are controlled by protein kinases. Phosphorylation of a positionally conserved tyrosine residue is obligatory for Stat dimerization, nuclear translocation, and specific DNA binding. Studies of Stat1 and Stat3 have suggested that serine phosphorylation may also regulate function. We now identify serine residues located in a conserved PSP motif of Stat5a (Ser725) and Stat5b (Ser730) as major phosphorylation sites, using mutagenesis, phosphoamino acid analysis, and site-specific anti-Stat5-phosphoserine antibodies. Unexpectedly, phosphorylation control of this PSP motif differed between the highly homologous Stat5a and Stat5b proteins. Whereas Ser725 of Stat5a was constitutively phosphorylated both in COS-7 cells and Nb2 lymphocytes, phosphorylation of Ser730 of Stat5b was markedly stimulated by prolactin. The data also suggested the existence of a second major serine phosphorylation site in Stat5a. Interestingly, constitutive phosphorylation of the PSP motif was suppressed by PD98059 but not by staurosporine under conditions in which both agents inhibited mitogen-activated protein kinases. Furthermore, pretreatment of cells with staurosporine, PD98059, H7, or wortmannin did not prevent either Stat5a or Stat5b from becoming maximally serine-phosphorylated after prolactin exposure. We propose that two pathways regulate Stat5 serine phosphorylation, one that is prolactin-activated and PD98059-resistant and one that is constitutively active and PD98059-sensitive and preferentially targets Stat5a. Finally, phosphorylation of the PSP motif of Stat5a or Stat5b was not essential for DNA binding or transcriptional activation of a beta-casein reporter gene in COS-7 cells, suggesting that serine kinase control of Stat5 activity differs from that of Stat1 and Stat3.

Alanine↗