The human semaphorin-like leukocyte cell surface molecule CD100 associates with a serine kinase activity.

CD100 is a 150-kDa homodimeric glycoprotein broadly expressed on the surface of human hematopoietic cells. CD100 has been recently identified as the first lymphoid gene that belongs to the semaphorin gene family. Semaphorins function as chemorepellent molecules in the nervous system, but the function of CD100 remains poorly understood. In lymphoid cells, it has been suggested to play a role in homotypic cell adhesion and in T cell activation. We demonstrate that in T cells and natural killer cells a serine kinase activity is immunoprecipitated with CD100. Distinct epitopes of CD100 have been defined with specific monoclonal antibodies, mediating opposite effects at the functional level, especially in T cells. The kinase activity is retained only with an antibody against a particular epitope of CD100. Additionally, a fusion protein containing the cytoplasmic domain of the molecule retains the kinase activity in cellular lysates, and CD100 itself is presumably a favorite substrate of the kinase. These findings suggest that a serine kinase pathway may participate in the different functional effects triggered through the distinct epitopes of CD100 and is likely involved in the biological effects of this semaphorin-like leukocyte cell surface molecule.