Tyrosine kinase growth factor receptors but not seven-membrane-spanning receptors or phorbol esters activate mitogen-activated protein kinase in rat hepatocytes

Pere Gines, Xiaomei Li, Jeffrey L. Zamarripa, Susan E S Brown, Eric Wieder, Toshikazu Nakamura, Phillip S. Guzelian, Robert W. Schrier, Lynn E. Heasley, Raphael A. Nemenoff

Research output: Contribution to journalArticle

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Abstract

The response of rat hepatocytes to hormones and growth factors has been extensively studied with respect to phospholipase regulation and calcium mobilization. However, the mitogen-activated protein (MAP) kinase cascade which integrates signals from a wide variety of extracellular stimuli has not been examined in these cells. Thus, in the present study the pathways leading to activation of MAP kinase in primary cultures of adult rat hepatocytes were investigated. Growth factors acting through tyrosine kinase receptors (epidermal growth factor and hepatocyte growth factor) increased Raf and MAP kinase activity through a protein kinase C and calcium-independent pathway. Agonists acting through seven-membrane-spanning receptors (arginine vasopressin and angiotensin II) increased intracellular calcium concentration but did not stimulate Raf or MAP kinase activity. Arginine vasopressin, however, stimulated MAP kinase activity in rat la fibroblasts transfected with the hepatic Via receptor and in rat aortic vascular smooth muscle cells. Phorbol 12-myristate 13-acetate (PMA) was also unable to stimulate Raf and MAP kinase in hepatocytes in spite of a marked activation of protein kinase C. We conclude that only signals arising from tyrosine kinase receptors are able to activate MAP kinase in hepatocytes. Neither agonists acting through seven-membrane-spanning receptors nor phorbol esters stimulate MAP kinase in hepatocytes. The results suggest that specific cellular components that link seven-membrane-spanning receptors with MAP kinase activation in tissues such as vascular smooth muscle are absent in rat hepatocytes.

Original languageEnglish (US)
Pages (from-to)1296-1303
Number of pages8
JournalHepatology
Volume22
Issue number4 PART 1
DOIs
StatePublished - 1995
Externally publishedYes

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Growth Factor Receptors
Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Hepatocytes
Membranes
Receptor Protein-Tyrosine Kinases
Vascular Smooth Muscle
Intercellular Signaling Peptides and Proteins
Calcium
phorbol ester receptor
Vasopressin Receptors
Hepatocyte Growth Factor
Phospholipases
Arginine Vasopressin
Epidermal Growth Factor
Angiotensin II
Protein Kinase C
Smooth Muscle Myocytes
Acetates
Fibroblasts

ASJC Scopus subject areas

  • Hepatology

Cite this

Tyrosine kinase growth factor receptors but not seven-membrane-spanning receptors or phorbol esters activate mitogen-activated protein kinase in rat hepatocytes. / Gines, Pere; Li, Xiaomei; Zamarripa, Jeffrey L.; Brown, Susan E S; Wieder, Eric; Nakamura, Toshikazu; Guzelian, Phillip S.; Schrier, Robert W.; Heasley, Lynn E.; Nemenoff, Raphael A.

In: Hepatology, Vol. 22, No. 4 PART 1, 1995, p. 1296-1303.

Research output: Contribution to journalArticle

Gines, P, Li, X, Zamarripa, JL, Brown, SES, Wieder, E, Nakamura, T, Guzelian, PS, Schrier, RW, Heasley, LE & Nemenoff, RA 1995, 'Tyrosine kinase growth factor receptors but not seven-membrane-spanning receptors or phorbol esters activate mitogen-activated protein kinase in rat hepatocytes', Hepatology, vol. 22, no. 4 PART 1, pp. 1296-1303. https://doi.org/10.1016/0270-9139(95)90642-8
Gines, Pere ; Li, Xiaomei ; Zamarripa, Jeffrey L. ; Brown, Susan E S ; Wieder, Eric ; Nakamura, Toshikazu ; Guzelian, Phillip S. ; Schrier, Robert W. ; Heasley, Lynn E. ; Nemenoff, Raphael A. / Tyrosine kinase growth factor receptors but not seven-membrane-spanning receptors or phorbol esters activate mitogen-activated protein kinase in rat hepatocytes. In: Hepatology. 1995 ; Vol. 22, No. 4 PART 1. pp. 1296-1303.
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AU - Brown, Susan E S

AU - Wieder, Eric

AU - Nakamura, Toshikazu

AU - Guzelian, Phillip S.

AU - Schrier, Robert W.

AU - Heasley, Lynn E.

AU - Nemenoff, Raphael A.

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