The proline-rich motif (PRM): a novel feature of the cytokine/hematopoietin receptor superfamily

Abstract

Members of the cytokine receptor superfamily have been grouped together by function and by the presence of conserved amino acids in the extracellular domain, including four cysteine residues and the Trp-Ser-X-Trp-Ser (WSXWS) motif. However, no consensus sequence motif has been described in the intracellular domain of the cytokine receptors. We now report the presence of a proline-rich consensus sequence motif, eight amino acids in length, which is found in the intracellular domain of all the cytokine receptors. The proline-rich motif (PRM) can be divided into two complementary families that have superimposable consensus sequences. The consensus sequences were found by allowing similar amino acids (aliphatic = Al, aromatic = Ar) to be grouped together. The first motif (PRM1) has the sequence Al-Ar-Pro-X-Al-Pro-X-Pro, while the second (PRM2) is Ar-X-X-X-Al-Pro-X-Pro. An overall consensus sequence for the PRM (PRM1 and PRM2) is derived by allowing aromatic and aliphatic residues to be considered hydrophobic (psi): psi-X-X-X-Al-Pro-X-Pro. Several alternative cytokine receptor isoforms contain two copies of the PRM within the same intracellular domain. The conservation of the proline-rich motif in cytokine receptors suggests that it plays a critical role in receptor function and defines a new feature of the cytokine receptor superfamily.