RGD Reference Report - The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes. - Rat Genome Database

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The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes.

Authors: Incoronato, M  D'Alessio, A  Paladino, S  Zurzolo, C  Carlomagno, MS  Cerchia, L  De Franciscis, V 
Citation: Incoronato M, etal., Cell Signal. 2004 Jul;16(7):847-56.
RGD ID: 1601572
Pubmed: PMID:15115663   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2004.01.002   (Journal Full-text)

The Shp-2 and Shp-1 non-transmembrane tyrosine phosphatases display different and even opposing effects on downstream signaling events initiated by Ret activation. By using rat pheochromocytoma-derived PC12 cells, here we studied the interactions of Shp-2 and Shp-1 with two activated mutants of Ret receptor, Ret(C634Y) and Ret(M918T). Each of these mutated receptors causes inheritance of distinct cancer syndromes, multiple endocrine neoplasia (MEN) type 2A and type 2B, respectively. We show that: (i) both Shp-1 and Shp-2 are associated to a multiprotein complex that includes Ret mutants; (ii) the Shp-1-Ret complexes are distinct from Shp-2-Ret complexes, and these complexes are differently distributed inside and outside lipid rafts; (iii) constitutively activated Ret proteins neither directly bind to nor are substrates of these phosphatases. Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
receptor tyrosine kinase binding  IPIRet (Rattus norvegicus)1601572 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptpn11  (protein tyrosine phosphatase, non-receptor type 11)

Objects referenced in this article
Gene Ret ret proto-oncogene Rattus norvegicus

Additional Information