The p21Ras GTPase activating protein-associated 62-kDa protein, p62Dok1, is an early substrate of various tyrosine phosphorylation pathways. Its recent cloning in human myeloid cells and in murine pre-B cells revealed an N-terminal pleckstrin-homology domain and a tyrosine- and proline-rich C-terminal tail in its sequence. Here, we characterized a new 1261-bp cDNA identical to that of p62Dok1, but with a central 185-bp deletion (bp 456-640). This induced a frameshift leading to a premature stop codon. The deduced protein, designated p22Dok(del), corresponded to a truncated p62Dok1 isoform of 177 amino acids that can be expressed both in vitro and in vivo with an apparent molecular mass of 22 kDa. This newly identified molecule was composed of the N-terminal PH domain of p62Dok1 followed by a new 25-amino acid C-terminal sequence containing a typical class II proline-rich motif, suggesting a specific role for p22Dok(del) in signal transduction pathways.