Evidence map›Paper›PMID 10716931›Full record

ArticleThe EMBO journal2000

Point mutation in kit receptor tyrosine kinase reveals essential roles for kit signaling in spermatogenesis and oogenesis without affecting other kit responses.

H Kissel, I Timokhina, M P Hardy, G Rothschild, Y Tajima, V Soares, M Angeles, S R Whitlow, K Manova, P Besmer

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed
9.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 359 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. c-KitCell death and differentiation · 2025
    Article
  5. Article
  6. Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Current progress onFrontiers in cell and developmental biology · 2023
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

H KisselMolecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
I Timokhina
M P Hardy
G Rothschild
Y Tajima
V Soares
M Angeles
S R Whitlow
K Manova
P Besmer
Memorial Sloan Kettering Cancer Center · US

Funding

CONTROL OF PROSTATE-SPECIFIC GENE EXPRESSIONR01DK055748 · NIDDK · VANDERBILT UNIVERSITY · PI MATUSIK, ROBERT J. · 1999 to 2013
$4.1M
PI 3-KINASE AND KIT RECEPTOR SIGNALINGR01HL055748 · NHLBI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI BESMER, PETER · 1997 to 2012
$4.0M
NORMAL FUNCTION AND ONCOGENIC ACTIVATIONR37CA032926 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI BESMER, PETER · 1991 to 1998
–
NCI NIH HHS R37 CA32926NHLBI NIH HHS HL/DK55748NIDDK NIH HHS R01 DK055748
6 · The paper itself

Abstract

The Kit receptor tyrosine kinase functions in hemato- poiesis, melanogenesis and gametogenesis. Kit receptor-mediated cellular responses include proliferation, survival, adhesion, secretion and differentiation. In mast cells, Kit-mediated recruitment and activation of phosphatidylinositol 3'-kinase (PI 3-kinase) produces phosphatidylinositol 3'-phosphates, plays a critical role in mediating cell adhesion and secretion and has contributory roles in mediating cell survival and proliferation. To investigate the consequences in vivo of blocking Kit-mediated PI 3-kinase activation we have mutated the binding site for the p85 subunit of PI 3-kinase in the Kit gene, using a knock-in strategy. Mutant mice have no pigment deficiency or impairment of steady-state hematopoiesis. However, gametogenesis is affected in several ways and tissue mast cell numbers are affected differentially. While primordial germ cells during embryonic development are not affected, Kit(Y719F)/Kit(Y719F) males are sterile due to a block at the premeiotic stages in spermatogenesis. Furthermore, adult males develop Leydig cell hyperplasia. The Leydig cell hyperplasia implies a role for Kit in Leydig cell differentiation and/or steroidogenesis. In mutant females follicle development is impaired at the cuboidal stages resulting in reduced fertility. Also, adult mutant females develop ovarian cysts and ovarian tubular hyperplasia. Therefore, a block in Kit receptor-mediated PI 3-kinase signaling may be compensated for in hematopoiesis, melanogenesis and primordial germ cell development, but is critical in spermatogenesis and oogenesis.

Indexed as

Signal TransductionAnimalsCell CountCells, CulturedFemaleGerm CellsHematopoiesisHyperplasiaInfertilityLeydig CellsMaleMast CellsMeiosisMelanocytesMiceMice, Inbred StrainsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-kit

Identifiers

PMID10716931
PMCPMC305672
OpenAlexW2168056910

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.