Faculty Collaboration Database

Growth signaling and JAK2 association mediated by membrane-proximal cytoplasmic regions of prolactin receptors. J Biol Chem 1994 Jul 15;269(28):18267-70

Date

07/15/1994

Pubmed ID

8034567

Scopus ID

2-s2.0-0028301226 (requires institutional sign-in at Scopus site)   143 Citations

Abstract

Prolactin (PRL) has recently been demonstrated to induce tyrosine phosphorylation and activation of the cytoplasmic tyrosine kinase JAK2 in PRL-dependent Nb2 lymphoma cells. The present study represents an initial effort to identify cytoplasmic regions of the PRL receptor (PRLR) that are critical to growth signal generation and JAK2 activation. Variably truncated rat PRLRs were stably expressed in the murine 32D cell line. PRL-induced proliferation was mediated by the full-length receptor and the mutant G328, which contains the membrane-proximal Homology Boxes 1 and 2 characteristic of hematopoietin receptors. In contrast, mutant receptors lacking either Box 2 or both Boxes 1 and 2 were not capable of transmitting a growth signal. The mitogenic capacity of the PRLR variants correlated with JAK2 association and activation, as well as with induction of mRNA levels for the growth-related gene ornithine decarboxylase. We conclude that mitogenic competence of rat PRLRs resides within the first 94 amino acids of the cytoplasmic domain. The data suggest that Homology Box 1/Box 2 region is critical to JAK2 phosphorylation and association with the PRLR. These findings will serve as a basis for more detailed molecular characterization of PRLR domains essential for JAK2 interaction and growth signal generation.

Author List

DaSilva L, Howard OM, Rui H, Kirken RA, Farrar WL

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Base Sequence
Cell Division
Cell Line
Cell Membrane
DNA Primers
Gene Expression
Humans
Interleukin-3
Janus Kinase 2
Mice
Molecular Sequence Data
Mutagenesis
Ornithine Decarboxylase
Plasmids
Polymerase Chain Reaction
Prolactin
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
RNA, Messenger
Rats
Receptors, Prolactin
Restriction Mapping
Sequence Deletion
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Signal Transduction
Transfection