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Titolo:
Activation of class IA PI3K stimulates DNA synthesis in human airway smooth muscle cells
Autore:
Krymskaya, VP; Ammit, AJ; Hoffman, RK; Eszterhas, AJ; Panettieri, RA;
Indirizzi:
Univ Penn, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Crit Care, Philadelphia, PA 19104 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
fascicolo: 5, volume: 280, anno: 2001,
pagine: L1009 - L1018
SICI:
1040-0605(200105)280:5<L1009:AOCIPS>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; KINASE; PROLIFERATION; PATHWAY; SUBUNIT; LOCALIZATION; SUFFICIENT; MECHANISMS; EXPRESSION;
Keywords:
phosphatidylinositol 3-kinase; airway remodeling; asthma; signaling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Krymskaya, VP Univ Penn, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care, Rm 847,BRB II-III,421 Curie Blvd, Philadelphia, PA 19104 USA Univ Penn Rm 847,BRB II-III,421 Curie Blvd Philadelphia PA USA 19104
Citazione:
V.P. Krymskaya et al., "Activation of class IA PI3K stimulates DNA synthesis in human airway smooth muscle cells", AM J P-LUNG, 280(5), 2001, pp. L1009-L1018

Abstract

The precise mechanisms that regulate increases in airway smooth muscle (ASM) mass in asthma are unknown. This study determined whether class IA phosphatidylinositol 3-kinase (PI3K) is sufficient to stimulate DNA synthesis and characterized the PI3K isoforms expressed in human ASM cells. ASM cells express class IA, II, and III PI3K but not class IB. Because thrombin induces ASM cell proliferation, we investigated whether thrombin can stimulate class IA PI3K. Transient transfection of ASM cells with hemagglutinin-tagged p85 PI3K followed by immunostaining revealed that in quiescent cells, p85 was expressed diffusely in the cytoplasm and after stimulation with thrombinp85 translocated to the cell membrane. Microinjection of ASM cells with a dominant negative class IA PI3K inhibited thrombin-induced DNA synthesis by30% and epidermal growth factor (EGF)- or serum-induced DNA synthesis by 13 and 28%, respectively (P < 0.05 by <chi>(2) analysis). In parallel experiments, transfection or microinjection of cells with constitutively active PI3K markedly increased DNA synthesis in transfected cells 10.5-fold and in microinjected cells 12.7-fold (P < 0.05 by <chi>(2) analysis) compared withcells transfected or microinjected with control plasmid. Interestingly, constitutively active PI3K augmented EGF-induced DNA synthesis but had littleeffect on that induced by serum or thrombin in ASM cells. Collectively, these data suggest that class IA PI3K is activated by thrombin and is sufficient to induce ASM cell growth.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 18:37:50