PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation

S Ali; Z Chen; J J Lebrun; W Vogel; A Kharitonenkov; P A Kelly; A Ullrich

PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation

EMBO J. 1996 Jan 2;15(1):135-42.

Authors

S Ali¹, Z Chen, J J Lebrun, W Vogel, A Kharitonenkov, P A Kelly, A Ullrich

Affiliation

¹ Department of Molecular Biology, Max-Planck-Institut fur Biochemie, Martinsried, Germany.

PMID: 8598196
PMCID: PMC449925

Abstract

Stimulation of the prolactin receptor (PRLR), a member of the cytokine/growth hormone receptor family, results in activation of the associated Jak2 tyrosine kinase and downstream signaling pathways. We report that PTP1D, a cytoplasmic protein tyrosine phosphatase containing two Src homology 2 (SH2) domains, physically associates with the PRLR-Jak2 complex and is tyrosine-phosphorylated upon stimulation with prolactin. The formation of the trimeric PRLR-Jak2-PTP1D complex is critical for transmission of a lactogenic signal, while PTP1D phosphorylation is necessary, but not sufficient. The dominant negative inhibitory effect of a phosphatase-deficient mutant on expression of a beta-casein promoter-controlled reporter gene is evidence for an essential role of fully functional PTP1D in the regulation of milk protein gene transcription.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Caseins / genetics*
Cells, Cultured
DNA Primers / chemistry
Enzyme Activation
Gene Expression Regulation
Humans
Intracellular Signaling Peptides and Proteins
Janus Kinase 2
Molecular Sequence Data
Phosphotyrosine / metabolism
Prolactin / physiology*
Promoter Regions, Genetic
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / physiology*
Protein-Tyrosine Kinases / metabolism*
Proto-Oncogene Proteins*
Receptors, Prolactin / physiology*
SH2 Domain-Containing Protein Tyrosine Phosphatases
Signal Transduction
Structure-Activity Relationship
src Homology Domains

Substances

Caseins
DNA Primers
Intracellular Signaling Peptides and Proteins
Proto-Oncogene Proteins
Receptors, Prolactin
Phosphotyrosine
Prolactin
Protein-Tyrosine Kinases
JAK2 protein, human
Janus Kinase 2
PTPN11 protein, human
PTPN6 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases
SH2 Domain-Containing Protein Tyrosine Phosphatases