Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2001-8-13
pubmed:abstractText
NIK, a recently identified Nck-interacting kinase, acts upstream of the MEK kinase MEKK1 to activate the c-Jun N-terminal kinase JNK. We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1. In a genetic screen, NHE1 interacted with NIK at a site N-terminal (amino acids 407-502) to the Nck-binding domain, and this site is critical for its association with NHE1 in vivo. NIK also phosphorylates NHE1; however, the phosphorylation sites, which are distal to amino acid 638, are distinct from the NIK-binding site on NHE1 (amino acids 538-638). Expression of wild-type, but not a kinase-inactive, NIK in fibroblasts increased NHE1 phosphorylation and activity. The kinase domain of NIK, however, was not sufficient for this response in vivo. Full phosphorylation and activation of NHE1 required both the kinase and the NHE1-binding domains of NIK, suggesting that the NHE1-binding site functions as a targeting signal. The functional significance of an interaction between NIK and NHE1 was confirmed by the ability of a kinase-inactive NIK to selectively inhibit activation of NHE1 by platelet-derived growth factor but not by thrombin. Moreover, although NIK activates JNK through a mechanism dependent on MEKK1, it phosphorylated and activated NHE1 independently of MEKK1. These findings indicate that NIK acts downstream of platelet-derived growth factor receptors to phosphorylate and activate NHE1 divergently of its activation of JNK.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31349-56
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.
pubmed:affiliation
Department of Stomatology, University of California, San Francisco 94143, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't