The Early Mitogenic Pathway in Mouse Thymocytes: An Analysis of the Dual Signal Hypothesis

  • James C. Metcalfe
  • Gerry A. Smith
  • John P. Moore
  • Robin Hesketh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 213)


The sequence of intercellular responses in mouse thymocytes to a polyclonal mitogen, such as concanavalin A (Con A), that are analyzed in this contribution are summarized in Table I. The earliest responses that free Ca2+ concentrations ([Ca2+]i) (1) within a few seconds of the addition of Con A and a coincident breakdown of phosphatidyl inositol (4,5) bisphosphate (PtdInsP2) to release inositol trisphosphate (InsP3) (2). These responses are followed by a rise in intracellular pH (pHi) (3) and increased synthesis of PtdInsp2 and its precursor, PtdInsP (2). After an approximately 10 time longer delay there is a large increase in the amount of mRNA of specific proto-oncogenes: a transient increase in c-fos mRNA (4) precedes the persistent increase in the amount of c-mvc mRNA (5). Over about the same time scale in G1 there is a general stimulation of metabolism marked, for example, by an increase in glycolysis (6), the transport of metabolites into the cell (uridine, etc., (7)) and the incorporation of inositol into PtdIns (8). These responses are followed later in G1 by a general increase in RNA and protein synthesis (9). The three groups of responses in Table I therefore provide markers of stages in progression through G1.


Inositol Phosphate Phosphatidyl Inositol Mitogenic Stimulation Mouse Thymocyte Mitogenic Pathway 
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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • James C. Metcalfe
    • 1
  • Gerry A. Smith
    • 1
  • John P. Moore
    • 1
  • Robin Hesketh
    • 1
  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK

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