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Updated: Feb 16, 2026

Monitoring Kinase and Phosphatase Activities Through the Cell Cycle by Ratiometric FRET
13:38

Monitoring Kinase and Phosphatase Activities Through the Cell Cycle by Ratiometric FRET

Published on: January 27, 2012

14.7K

Maintenance of murine platelet homeostasis by the kinase Csk and phosphatase CD148

Jun Mori1, Zoltan Nagy1, Giada Di Nunzio1

  • 1Institute of Cardiovascular Sciences and.

Blood
|January 6, 2018
PubMed

Insights

C-terminal Src kinase (Csk) and CD148 regulate platelet reactivity by controlling Src family kinases (SFKs). Their absence paradoxically reduces thrombus formation, revealing feedback mechanisms preventing excessive clotting.

Area of Science:

  • Hematology
  • Molecular Biology
  • Biochemistry

Background:

  • Src family kinases (SFKs) are crucial for platelet activation signaling.
  • Regulation of SFKs in platelets is not fully understood.
  • C-terminal Src kinase (Csk) and CD148 are implicated as potential regulators.

Purpose of the Study:

  • To investigate the roles of Csk and CD148 in regulating platelet SFK activity and function.
  • To elucidate the molecular mechanisms by which Csk and CD148 control platelet reactivity and hemostasis.
  • To understand the feedback mechanisms involved in preventing pathological thrombosis.

Main Methods:

  • Genetic ablation of Csk and CD148 in mice.
  • Analysis of platelet SFK activity in knockout mice.
  • Assessment of in vivo and ex vivo thrombus formation and bleeding.
  • Investigation of ITAM- and ITIM-containing receptor expression and signaling.
  • Utilizing an analog-sensitive Csk mouse model.

Main Results:

  • Ablation of Csk and CD148 led to increased platelet SFK activity.
  • Csk/CD148-deficient mice showed reduced thrombus formation and increased bleeding.
  • Negative feedback mechanisms involved downregulation of activating receptors (GPVI, CLEC-2) and upregulation of inhibitory receptors (G6b-B) with phosphatases (Shp1, Shp2).
  • SFKs were found to activate ITIM signaling.

Conclusions:

  • Csk and CD148 are critical regulators of platelet SFK activity and essential molecular switches for hemostasis and thrombosis.
  • Cell-intrinsic feedback mechanisms controlled by Csk and CD148 prevent pathological thrombosis.
  • This study reveals novel insights into platelet signaling and regulation.

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