The CD53 antigen is a member of the tetraspanin membrane protein family that is expressed in the lymphoid-myeloid lineage. We have studied the implication of CD53 antigen in signal transduction by determining the effect of its ligation on the c-Jun N-terminal kinase (JNK) in different cell types. Ligation of the rat or human CD53 antigen induces a threeto fourfold transient activation of JNK activity that peaks at 3–5 min. The effect was detected by assaying the endogenous or exogenous (transfected) JNK activity