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Identification of phospholipase C-gamma1 as a mitogen-activated protein kinase substrate.
Buckley, Colin T; Sekiya, Fujio; Kim, Yeun Ju; Rhee, Sue Goo; Caldwell, Kevin K.
Afiliação
  • Buckley CT; Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA.
J Biol Chem ; 279(40): 41807-14, 2004 Oct 01.
Article em En | MEDLINE | ID: mdl-15258148
ABSTRACT
The discovery of sequence motifs that mediate protein-protein interactions, coupled with the availability of protein amino acid sequence data, allows for the identification of putative protein binding pairs. The present studies were based on our identification of an amino acid sequence in phosphatidylinositol-specific phospholipase C-gamma1 (PLC-gamma1) that fits the consensus sequence for a mitogen-activated protein kinase (MAPK) binding site, termed the D-domain. Extracellular signal-regulated kinase 2 (ERK2), an MAPK, and phospho-ERK2 were bound by an immobilized peptide sequence containing the identified PLC-gamma1 D-domain. Furthermore, a peptide containing the PLC-gamma1 D-domain was able to competitively inhibit the in vitro phosphorylation of recombinant PLC-gamma1 by recombinant phospho-ERK2, whereas a control peptide derived from a distant region of PLC-gamma1 was ineffective. Similarly, the peptide containing the PLC-gamma1 D-domain, but not the control peptide, competitively inhibited the in vitro phosphorylation of Elk-1 and c-Jun catalyzed by recombinant phospho-ERK2 and phospho-c-Jun N-terminal kinase 3 (phospho-JNK3), another type of MAPK, respectively. Incubation of anti-PLC-gamma1 immunocomplexes isolated from rat brain with recombinant phospho-ERK2 opposed the increase in PLC-gamma1-catalyzed hydrolysis of phosphatidylinositol 4,5-P(2) (PtdIns(4,5)P(2)), which was produced by a tyrosine kinase associated with the immunocomplexes, whereas in vitro phosphorylation of recombinant PLC-gamma1 by recombinant phospho-ERK2 did not alter PLC-gamma1-catalyzed PtdIns(4,5)P(2) hydrolysis. These studies have uncovered a previously unidentified mechanism for the integration of PLC-gamma1- and ERK2-dependent signaling.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipases Tipo C / Proteína Quinase 1 Ativada por Mitógeno / Receptor Cross-Talk Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: J Biol Chem Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipases Tipo C / Proteína Quinase 1 Ativada por Mitógeno / Receptor Cross-Talk Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: J Biol Chem Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Estados Unidos