BMX, A NOVEL NONRECEPTOR TYROSINE KINASE GENE OF THE BTK ITK/TEC/TXK FAMILY LOCATED IN CHROMOSOME XP22.2/

The Bmx sequence was identified and cloned during our search for novel tyrosine kinase genes expressed in human bone marrow cells. Bmx cDNA comprises a long open reading frame of 675 amino acids, containing one SH3, one SH2 and one tyrosine kinase domain, which are about 70% iden tical with Btk, Itk and Tec and somewhat less with Txk tyrosine kinase sequences. The amino terminal sequences of these four tyrosine kinase s are about 40% identical and each contains a so-called pleckstrin hom ology domain. The 2.7 kb Bmx mRNA was expressed in endothelial cells a nd several human tissues by Northern blotting and an 80 kD Bmx polypep tide was detected in human endothelial cells. Immunoprecipitates of CO S cells transfected with a Bmx expression vector and NIH3T3 cells expr essing a Bmx retrovirus contained a tyrosyl phosphorylated Bmx polypep tide of similar molecular weight. The BMX gene was located in chromoso mal band Xp22.2 between the DXS197 and DXS207 loci. Interestingly, chr omosome X also contains the closest relative of BMX, the BTK gene, imp licated in X-linked agammaglobulinemia. The BMX gene thus encodes a no vel nonreceptor tyrosine kinase, which may play a role;in the growth a nd differentiation of hematopoietic cells.