The CRK/CRKL SH2-domain directly binds phosphorylated Y463-FGFR1 [47,48] and can interact with FRS2-GRB2-PTPN11 [49] in a complex containing SHC, breast cancer anti-estrogen resistance protein 1 (BCAR1) and RAP guanine nucleotide exchange factor 1 (RAPGEF1) (Figure 2) [47] to regulate efficient activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) of the RAS-MAPK pathway [48,50]. This evidence concerns the gene RAPGEF1 and breast carcinoma.