logo
CanyamAI summaries for academic research
language
MobileMobile
  • Phone FeatureWeChat Mini Program
EnglishEnglish
noticeNotice
BlogBlog
delete
arrow
Return

T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation

delete2023-03-27
delete65
delete
OA
AI
P
Paul D. Simoncic
A
Annie Bourdeau
A
Ailsa Lee-Loy
L
Larry R. Rohrschneider
M
Michel L. Tremblay
E
E. Richard Stanley
C
C. Jane McGlade *
DOI：10.1128/MCB.01932-05delete
deleteOriginal
deleteShare
deleteSave
View PDF
Abstract

Abstract

En 中文
Mice null for the T-cell protein tyrosine phosphatase (Tcptp(-/-)) die shortly after birth due to complications arising from the development of a systemic inflammatory disease. It was originally reported that Tcptp-/- Mice have increased numbers of macrophages in the spleen; however, the mechanism underlying the aberrant growth and differentiation of macrophages in Teptp(-/-) mice is not known. We have identified Tcptp as an important regulator of colony-stimulating factor 1 (CSF-1) signaling and mononuclear phagocyte development. The number of CSF-1-dependent CFU is increased in Tcptp(-/-) bone marrow. Tcptp(-/-) mice also have increased numbers of granulocyte-macrophage precursors (GMP), and these Tcptp(-/-) GMP yield more macrophage colonies in response to CSF-1 relative to wild-type cells. Furthermore, we have identified the CSF-1 receptor (CSF-IR) as a physiological target of Tcptp through substrate-trapping experiments and its hyperphosphorylation in Tcptp(-/-) macrophages. Tcptp(-/-) macrophages also have increased tyrosine phosphorylation and recruitment of a Grb2/Gab2/Shp2 complex to the CSF-1R and enhanced activation of Erk after CSF-1 stimulation, which are important molecular events in CSF-1-induced differentiation. These data implicate Tcptp as a critical regulator of CSF-1 signaling and mononuclear phagocyte development in hematopoiesis.
Keywords:
SRC FAMILY KINASES
BONE-MARROW CELLS
M-CSF RECEPTOR
FACTOR-I
SCAFFOLDING PROTEIN
FDC-P1 CELLS
PHOSPHORYLATION
ASSOCIATION
ACTIVATION
DEFICIENT
AI Summary

AI Summary

Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.

Journal

Molecular and Cellular Biology cover
Molecular and Cellular Biology
IF:
2.7
Papers:
1.3W
Citations:
3.8W

Organization

No organization information available