Impaired Crkl expression contributes to the defective DNA binding of Stat5b in nonobese diabetic mice

Malini Laloraya, Abdoreza Davoodi-Semiromi, G. Pradeep Kumar, Marcia McDuffie, Jin-Xiong She

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A point mutation in the Stat5b DNA binding domain in the nonobese diabetic (NOD) mouse was shown to have weaker DNA binding compared with the B6 Stat5b. Here, we assessed the binding ability of the mutant Stat5b in the B6 genetic background (B6.NOD-c11) and the wild-type Stat5b in the NOD background (NOD.Lc11). To our surprise, the binding ability of Stat5b is inconsistent with the presence or absence of the Stat5b mutation in these congenic mice but is correlated with the expression levels of the Crkl protein, which was coprecipitated by an anti-Stat5b antibody. Both the expression of Crkl and the Stat5b binding ability are the highest in B6.NOD-c11 and the lowest in NOD while intermediate in B6 and NOD.Lc11 mice. We demonstrated that the adapter molecule Crkl can bind Stat5b and that the Crkl protein is a Stat5b binding cofactor. More importantly, profection of Crkl recombinant protein significantly increased Stat5b binding ability and rescued the binding defect of the NOD mutant Stat5b, suggesting that Crkl is a key regulatory molecule for Stat5b binding. Therefore, the defective Crkl expression may contribute to the development of diabetes in the NOD mice by exacerbating the defective Stat5b binding ability.

Original languageEnglish (US)
Pages (from-to)734-741
Number of pages8
JournalDiabetes
Volume55
Issue number3
DOIs
StatePublished - Jan 1 2006

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Inbred NOD Mouse
Congenic Mice
DNA
Point Mutation
Recombinant Proteins
Anti-Idiotypic Antibodies
Proteins
Mutation
Genetic Background

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Impaired Crkl expression contributes to the defective DNA binding of Stat5b in nonobese diabetic mice. / Laloraya, Malini; Davoodi-Semiromi, Abdoreza; Kumar, G. Pradeep; McDuffie, Marcia; She, Jin-Xiong.

In: Diabetes, Vol. 55, No. 3, 01.01.2006, p. 734-741.

Research output: Contribution to journalArticle

Laloraya, Malini ; Davoodi-Semiromi, Abdoreza ; Kumar, G. Pradeep ; McDuffie, Marcia ; She, Jin-Xiong. / Impaired Crkl expression contributes to the defective DNA binding of Stat5b in nonobese diabetic mice. In: Diabetes. 2006 ; Vol. 55, No. 3. pp. 734-741.
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