RGD Reference Report - JAK/STAT signal transduction: regulators and implication in hematological malignancies. - Rat Genome Database

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JAK/STAT signal transduction: regulators and implication in hematological malignancies.

Authors: Valentino, L  Pierre, J 
Citation: Valentino L and Pierre J, Biochem Pharmacol. 2006 Mar 14;71(6):713-21. Epub 2006 Jan 19.
RGD ID: 2290530
Pubmed: PMID:16426581   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bcp.2005.12.017   (Journal Full-text)

Signal transducers and activators of transcription (STATs) comprise a family of several transcription factors that are activated by a variety of cytokines, hormones and growth factors. STATs are activated through tyrosine phosphorylation, mainly by JAK kinases, which lead to their dimerization, nuclear translocation and regulation of target genes expression. Stringent mechanisms of signal attenuation are essential for insuring appropriate, controlled cellular responses. Among them phosphotyrosine phosphatases (SHPs, CD45, PTP1B/TC-PTP), protein inhibitors of activated STATs (PIAS) and suppressors of cytokine signaling (SOCS) inhibit specific and distinct aspects of cytokine signal transduction. SOCS proteins bind through their SH2 domain to phosphotyrosine residues in either cytokine receptors or JAK and thus can suppress cytokine signaling. Many recent findings indicate that SOCS proteins act, in addition, as adaptors that regulate the turnover of certain substrates by interacting with and activating an E3 ubiquitin ligase. Thus, SOCS proteins act as negative regulators of JAK/STAT pathways and may represent tumour suppressor genes. The discovery of oncogenic partner in this signaling pathway, more especially in diverse hematologic malignancies support a prominent role of deregulated pathways in the pathogenesis of diseases. Fusion proteins implicating the JH1 domain of JAK2 (TEL-JAK2, BCR-JAK2), leading to deregulated activity of JAK2, have been described as the result of translocation. Somatic point mutation in JH2 domain of JAK2 (JAK2V617F), leading also to constitutive tyrosine phosphorylation of JAK2 and its downstream effectors was reported in myeloproliferative disorders. Furthermore, silencing of socs-1 and shp-1 expression by gene methylation is observed in some cancer cells.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PIAS1HumanJak-Stat signaling pathway   TAS  RGD 
PIAS2HumanJak-Stat signaling pathway   TAS  RGD 
PIAS3HumanJak-Stat signaling pathway   TAS  RGD 
PIAS4HumanJak-Stat signaling pathway   TAS  RGD 
PTPN1HumanJak-Stat signaling pathway   TAS  RGD 
PTPN11HumanJak-Stat signaling pathway   TAS  RGD 
PTPN2HumanJak-Stat signaling pathway   TAS  RGD 
PTPN6HumanJak-Stat signaling pathway   TAS  RGD 
Pias1RatJak-Stat signaling pathway   ISOPIAS1 (Homo sapiens) RGD 
Pias1MouseJak-Stat signaling pathway   ISOPIAS1 (Homo sapiens) RGD 
Pias2RatJak-Stat signaling pathway   ISOPIAS2 (Homo sapiens) RGD 
Pias2MouseJak-Stat signaling pathway   ISOPIAS2 (Homo sapiens) RGD 
Pias3RatJak-Stat signaling pathway   ISOPIAS3 (Homo sapiens) RGD 
Pias3MouseJak-Stat signaling pathway   ISOPIAS3 (Homo sapiens) RGD 
Pias4RatJak-Stat signaling pathway   ISOPIAS4 (Homo sapiens) RGD 
Pias4MouseJak-Stat signaling pathway   ISOPIAS4 (Homo sapiens) RGD 
Ptpn1RatJak-Stat signaling pathway   ISOPTPN1 (Homo sapiens) RGD 
Ptpn1MouseJak-Stat signaling pathway   ISOPTPN1 (Homo sapiens) RGD 
Ptpn11RatJak-Stat signaling pathway   ISOPTPN11 (Homo sapiens) RGD 
Ptpn11MouseJak-Stat signaling pathway   ISOPTPN11 (Homo sapiens) RGD 
Ptpn2RatJak-Stat signaling pathway   ISOPTPN2 (Homo sapiens) RGD 
Ptpn2MouseJak-Stat signaling pathway   ISOPTPN2 (Homo sapiens) RGD 
Ptpn6RatJak-Stat signaling pathway   ISOPTPN6 (Homo sapiens) RGD 
Ptpn6MouseJak-Stat signaling pathway   ISOPTPN6 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Pias1  (protein inhibitor of activated STAT, 1)
Pias2  (protein inhibitor of activated STAT, 2)
Pias3  (protein inhibitor of activated STAT, 3)
Pias4  (protein inhibitor of activated STAT, 4)
Ptpn1  (protein tyrosine phosphatase, non-receptor type 1)
Ptpn11  (protein tyrosine phosphatase, non-receptor type 11)
Ptpn2  (protein tyrosine phosphatase, non-receptor type 2)
Ptpn6  (protein tyrosine phosphatase, non-receptor type 6)

Genes (Mus musculus)
Pias1  (protein inhibitor of activated STAT 1)
Pias2  (protein inhibitor of activated STAT 2)
Pias3  (protein inhibitor of activated STAT 3)
Pias4  (protein inhibitor of activated STAT 4)
Ptpn1  (protein tyrosine phosphatase, non-receptor type 1)
Ptpn11  (protein tyrosine phosphatase, non-receptor type 11)
Ptpn2  (protein tyrosine phosphatase, non-receptor type 2)
Ptpn6  (protein tyrosine phosphatase, non-receptor type 6)

Genes (Homo sapiens)
PIAS1  (protein inhibitor of activated STAT 1)
PIAS2  (protein inhibitor of activated STAT 2)
PIAS3  (protein inhibitor of activated STAT 3)
PIAS4  (protein inhibitor of activated STAT 4)
PTPN1  (protein tyrosine phosphatase non-receptor type 1)
PTPN11  (protein tyrosine phosphatase non-receptor type 11)
PTPN2  (protein tyrosine phosphatase non-receptor type 2)
PTPN6  (protein tyrosine phosphatase non-receptor type 6)


Additional Information