RGD Reference Report - Requirement of Ca(2+) and PKCdelta for Janus kinase 2 activation by angiotensin II: involvement of PYK2. - Rat Genome Database

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Requirement of Ca(2+) and PKCdelta for Janus kinase 2 activation by angiotensin II: involvement of PYK2.

Authors: Frank, GD  Saito, S  Motley, ED  Sasaki, T  Ohba, M  Kuroki, T  Inagami, T  Eguchi, S 
Citation: Frank GD, etal., Mol Endocrinol 2002 Feb;16(2):367-77.
RGD ID: 633057
Pubmed: PMID:11818507   (View Abstract at PubMed)
DOI: DOI:10.1210/mend.16.2.0768   (Journal Full-text)

In vascular smooth muscle cells, angiotensin II (AngII) stimulates association of its G protein-coupled AngII type 1 (AT(1)) receptor with Janus kinase 2 (JAK2), resulting in the activation of signal transducer and activator of transcription proteins. Although the association and activation of subsequent signal transducer and activator of transcription proteins appear to prerequire JAK2 activation, the signaling mechanism by which the AT(1) receptor activates JAK2 remains uncertain. Here, we have examined the signaling mechanism required for JAK2 activation by AngII in vascular smooth muscle cells. We found that AngII, through the AT(1) receptor, rapidly stimulated JAK2 phosphorylation at Tyr(1007/1008), the critical sites for the kinase activation. By using selective agonists and inhibitors, we demonstrated that PLC and its derived signaling molecules, phosphatidylinositol triphosphate/Ca(2+) and diacylglycerol/PKC, were essential for AngII-induced JAK2 phosphorylation. The PKC isoform required for JAK2 activation appears to be PKCdelta since a selective PKCdelta but not PKCalpha/beta inhibitor and dominant-negative PKCdelta overexpression inhibited JAK2 activation. We further examined a link between JAK2 and a Ca(2+)/PKC-sensitive tyrosine kinase, PYK2. We found that PYK2 activation by AngII requires PKCdelta, and that PYK2 associates with JAK2 constitutively. Moreover, transfection of two distinct PYK2 dominant-negative mutants markedly inhibited AngII-induced JAK2 activation. From these data we conclude that AT(1)-derived signaling molecules, specifically Ca(2+) and PKCdelta, participate in AngII-induced JAK2 activation through PYK2. These data provide a new mechanistic insight by which the hormone AngII exerts its cytokine-like actions in mediating vascular remodeling.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
activation of Janus kinase activity  IMP 633057 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Jak-Stat signaling pathway   IMP 633057 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ptk2b  (protein tyrosine kinase 2 beta)

Objects referenced in this article
Gene Jak2 Janus kinase 2 Rattus norvegicus
Gene Prkcd protein kinase C, delta Rattus norvegicus

Additional Information