THE PROLINE-RICH MOTIF (PRM) - A NOVEL FEATURE OF THE CYTOKINE HEMATOPOIETIN RECEPTOR SUPERFAMILY

Members of the cytokine receptor superfamily have been grouped togethe r by function and by the presence of conserved amino acids in the extr acellular domain, including four cysteine residues and the Trp-Ser-X-T rp-Ser (WSXWS) motif. However, no consensus sequence motif has been de scribed 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 a ll the cytokine receptors. The proline-rich motif (PRM) can be divided into two complementary families that have superimposable consensus se quences. The consensus sequences were found by allowing similar amino acids (aliphatic = Al, aromatic = Ar) to be grouped together. The firs t motif (PRM1) has the sequence Al-Ar-Pro-X-Al-Pro-X-Pro, while the se cond (PRM2) is Ar-X-X-X-Al-Pro-X-Pro. An overall consensus sequence fo r the PRM (PRM1 and PRM2) is derived by allowing aromatic and aliphati c 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 crit ical role in receptor function and defines a new feature of the cytoki ne receptor superfamily.