Disease relevance of Crkl

• The SH2/SH3 adaptor protein Crkl is abnormally phosphorylated on tyrosine by the Bcr/Abl protein in leukemic cells from patients with Philadelphia-chromosome (Ph)positive leukemia [1].

High impact information on Crkl

• Impaired Crkl expression contributes to the defective DNA binding of Stat5b in nonobese diabetic mice [2].
• These included changes on Crkl, Ras-GAP-binding protein 1, and for BCR/ABL, cytoskeletal proteins such as tubulin, and Nedd5 [3].
• The Crkl SH2 domain binds specifically to Cbl [4].
• In the current study we show that Crkl, but only a minor amount of the related Crk, form constitutive complexes in vivo with guanine nucleotide exchange factor C3G in 3T3 fibroblasts [5].
• Tyrosine phosphorylation of proteins associated with such signalling complexes can generate binding sites for the Crkl SH2-domain and can recruit proteins constitutively bound to Crkl via the Crkl SH3 domain into such complexes [5].

Biological context of Crkl

• Tyrosine phosphorylation of murine Crkl [1].
• However Crkl, another gene implicated in the 22q11DS phenotype, was found to be downregulated by microarray and RTQPCR [6].
• The SH2-SH3 adaptor protein Crkl has been implicated in the signal transduction pathways of several membrane-bound receptors [5].

Enzymatic interactions of Crkl

• Crkl is complexed with tyrosine-phosphorylated Cbl in Ph-positive leukemia [4].

Other interactions of Crkl

• Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes [7].
• 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 [2].

References