Are there more members of the CNTF-GPA family?

Ciliary neurotrophic factor (CNTF) and growth promoting activity (GPA) are two members of a family of structurally and functionally related cytokines. Although the primary sequences of these proteins are only distantly related, many share striking functional similarities. The question of the potential existence of more, as yet undiscovered, members of this family, especially those most related to CNTF, is discussed. There are several biological systems which exhibit unexplained CNTF-like activities. This has led to speculation that there are indeed other CNTF-like proteins to be found. Because of the poor primary sequence conservation among known members of this family, even those sharing strong functional similarities, it is unlikely that a cloning approach based on sequence homology will find these putative new members of the family. Instead, a more biological approach, based on functional similarities, is more likely to succeed.