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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-2-22
pubmed:abstractText
We previously demonstrated that stimulation of human T-lymphocytes with calcium ionophores induced the phosphorylation and enzymatic activation of ERK2. We now report on the mechanism by which calcium-ionophore-induced activation of ERK1 and 2 occurs in these cells. The activation of ERK1 and 2 by increases in intracellular calcium was inhibited by calmidazolium suggesting the involvement of calmodulin in this response. To further elucidate the mechanism by which calcium-induced ERK activation occurs, we used the CaM-kinase inhibitor KN-93 and an inactive analog of KN-93 (KN-92). KN-93, but not KN-92, blocked ionomycin-induced activation of ERK1 and 2 in human T lymphocytes. We previously demonstrated that stimulation of T lymphocytes with ionomycin or A23187 resulted in a CaM-kinase-dependent shift in the mobility of p56(Lck). To determine if p56(Lck) was involved in calcium-induced ERK activation, we stimulated the p56(Lck) negative Jurkat cell derivatives, J.CaM1.6 and J.CaM1/Rep3, with ionomycin. In these p56(Lck) negative cell lines, activation of ERK1 and 2 in response to ionomycin was only minimally detected. When J.CaM1 cells were reconstituted with p56(Lck), ionomycin induced ERK1 and 2 activation. Treatment of Jurkat cells with PP2, an inhibitor of p56(Lck), inhibited calcium-induced, but not PMA-induced, ERK1 and 2 activation. Treatment of Jurkat cells with the MEK inhibitor PD98059 blocked ionomycin-induced ERK activation, but not the shift in the mobility of p56(Lck). Our data suggests that increases in intracellular calcium induce the activation of ERK1 and 2 in human T lymphocytes via sequential activation of CaM-kinase and phosphorylation of p56(Lck).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
675-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Calcium-induced ERK activation in human T lymphocytes occurs via p56(Lck) and CaM-kinase.
pubmed:affiliation
Department of Microbiology and Immunology, East Carolina University School of Medicine, Brody Building, Greenville, NC 27858, USA. franklinr@mail.ecu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't