What they found

Foundational paper identifying Ser133 as the PKA phosphorylation site on CREB and demonstrating that pCREB activates the somatostatin CRE. Established the PKA→CREB→CRE transcriptional cascade. Does not directly measure dephosphorylation kinetics of pCREB in cochlear hair cells.

Numbers that matter

  • PKA phosphorylates CREB at Ser133: confirmed
  • Dephosphorylation half-life of pCREB: t½ ~5–10 min in HeLa/COS cells (later work by the Montminy lab and others; not directly measured in this 1989 paper)
  • t½ 5–10 min → k_dephos = 0.0012–0.0023/s
  • The h05 model uses K_CREB_DEPHOS_S = 0.005/s (t½ 2.3 min) and cites this paper — a 2–4× discrepancy. The model dephosphorylates CREB faster than Gonzalez & Montminy’s data implies.
  • Hair cell-specific CREB-P kinetics not measured anywhere; the 2–4× discrepancy may be acceptable given tissue differences, but should be flagged.

Fit to h05

The citation is real and correct for the CREB phosphorylation mechanism. However, the specific rate constant K_CREB_DEPHOS_S = 0.005/s is faster than the cited t½ range implies. This should be explicitly noted as a deviation. A sensitivity analysis varying this parameter by 4× is warranted.

Connections