β-Hexosaminidase-induced activation of p44/42 mitogen-activated protein kinase is dependent on p21Ras and protein kinase C and mediates bovine airway smooth-muscle proliferation

D. Betty Lew, B. Kinard Dempsey, Yuling Zhao, Mubarek Muthalif, Soghra Fatima, Kafait Malik

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Late-phase and sustained activation of p44/42MAPK has been reported to be a critical factor in cell mitogenesis. We therefore hypothesized that p44/42MAPK is involved in mannosyl-rich glycoprotein-induced mitogenesis in bovine airway smooth-muscle cells (ASMC). Treatment of adherent ASMC with β-hexosaminidase A (Hex A, 50 nM), an endogenous mannosyl-rich glycoprotein, resulted in a late-onset (30-min) activation of p44/42MAPK that lasted for 4 h. Activation of p44/42MAPK induced by Hex A was inhibited by an 18-mer phosphorothioate-derivatized antisense oligonucleotide (1-5 μM ) directed to human p44MAPK; the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059 (5 μM); the p42MAPK inhibitor Tyrphostin AG-126 (0.2 μM); the farnesyl transferase inhibitors SCH-56582 (10 μM) and FPT III (10 μM), which inhibit p21Ras activation; and Calphostin C (0.2 μM), an inhibitor of protein kinase C. These agents also inhibited Hex A-induced cell proliferation in bovine ASMC. These data suggest that Hex A activates p44/42MAPK in a p21Ras-and PKC-dependent manner and that this activation mediates Hex A-induced mitogenesis in bovine ASMC.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume21
Issue number1
DOIs
StatePublished - Jan 1 1999

Fingerprint

Hexosaminidase A
Hexosaminidases
Mitogen-Activated Protein Kinases
Protein Kinase C
Smooth Muscle
Muscle
Chemical activation
Smooth Muscle Myocytes
Glycoproteins
Cells
Antisense Oligonucleotides
Mitogen-Activated Protein Kinase Kinases
Cell proliferation
Transferases
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

β-Hexosaminidase-induced activation of p44/42 mitogen-activated protein kinase is dependent on p21Ras and protein kinase C and mediates bovine airway smooth-muscle proliferation. / Lew, D. Betty; Dempsey, B. Kinard; Zhao, Yuling; Muthalif, Mubarek; Fatima, Soghra; Malik, Kafait.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 21, No. 1, 01.01.1999, p. 111-118.

Research output: Contribution to journalArticle

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abstract = "Late-phase and sustained activation of p44/42MAPK has been reported to be a critical factor in cell mitogenesis. We therefore hypothesized that p44/42MAPK is involved in mannosyl-rich glycoprotein-induced mitogenesis in bovine airway smooth-muscle cells (ASMC). Treatment of adherent ASMC with β-hexosaminidase A (Hex A, 50 nM), an endogenous mannosyl-rich glycoprotein, resulted in a late-onset (30-min) activation of p44/42MAPK that lasted for 4 h. Activation of p44/42MAPK induced by Hex A was inhibited by an 18-mer phosphorothioate-derivatized antisense oligonucleotide (1-5 μM ) directed to human p44MAPK; the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059 (5 μM); the p42MAPK inhibitor Tyrphostin AG-126 (0.2 μM); the farnesyl transferase inhibitors SCH-56582 (10 μM) and FPT III (10 μM), which inhibit p21Ras activation; and Calphostin C (0.2 μM), an inhibitor of protein kinase C. These agents also inhibited Hex A-induced cell proliferation in bovine ASMC. These data suggest that Hex A activates p44/42MAPK in a p21Ras-and PKC-dependent manner and that this activation mediates Hex A-induced mitogenesis in bovine ASMC.",
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